SRPX

Gene Summary

Gene:SRPX; sushi repeat containing protein X-linked
Aliases: DRS, ETX1, SRPX1, HEL-S-83p
Location:Xp11.4
Summary:-
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:sushi repeat-containing protein SRPX
Source:NCBIAccessed: 29 August, 2019

Ontology:

What does this gene/protein do?
SRPX is implicated in:
- cell adhesion
- cell surface
- membrane
Data from Gene Ontology via CGAP

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 29 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Srpx protein, rat
  • RTPCR
  • Oligonucleotide Array Sequence Analysis
  • Gene Expression Profiling
  • Down-Regulation
  • Amino Acid Sequence
  • Nuclear Proteins
  • Tumor Suppressor Proteins
  • lactate dehydrogenase 1
  • Tissue Distribution
  • FOXM1
  • Squamous Cell Carcinoma of Head and Neck
  • Small Cell Lung Cancer
  • Twist-Related Protein 1
  • Repetitive Sequences, Nucleic Acid
  • In Situ Hybridization
  • X Chromosome
  • Cell Cycle Proteins
  • Tissue Plasminogen Activator
  • Sequence Homology
  • Up-Regulation
  • Base Sequence
  • TWIST1
  • BNIP3
  • Molecular Sequence Data
  • Consensus Sequence
  • SRPX
  • Cell Proliferation
  • Cancer Gene Expression Regulation
  • Genome-Wide Association Study
  • Adenocarcinoma
  • SPARC
  • MicroRNAs
  • Tumor Suppressor Gene
  • Lung Cancer
  • Northern Blotting
  • Messenger RNA
  • Southern Blotting
  • siRNA
  • Membrane Proteins
  • Multiple Myeloma
  • Bladder Cancer
  • Prostate Cancer
Tag cloud generated 29 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: SRPX (cancer-related)

Guesmi F, Ben Hmed M, Prasad S, et al.
In vivo pathogenesis of colon carcinoma and its suppression by hydrophilic fractions of Clematis flammula via activation of TRAIL death machinery (DRs) expression.
Biomed Pharmacother. 2019; 109:2182-2191 [PubMed] Related Publications
This work focused on characterizing hydrophilic fractions of Clematis flammula (CFl). The data here clearly demonstrated that hydrolate fractions act as a free radical scavengers and inhibited proliferation of different cell lines in a time- and concentration-dependent manner, transwell, and with a significant cytotoxic effect. Treating cells with CFl had the effect of suppressing cell growth attenuated by ROS generation in colonic carcinoma. Moreover, CFl in HCT116 cells suppressed survival, proliferation, invasion, angiogenesis and metastasis in vitro by inhibiting gene expression. Following CFl treatment, caspases and PARP cleavage were detected. The up- and down-regulated genes obtained from the WBA of the effect of CFl showed that several biological processes were associated with apoptosis and induction of G1 cell cycle arrest. CFl synergizes the effect of TRAIL by down-regulating the expression of cell survival proteins involved in apoptosis compared to cells treated with CFl or TRAIL alone. Our findings showed that CFl sensitizes apoptosis in TRAIL-resistant cells by activating MAPKs, SP1, and CHOP, that induced DR5 expression. Overall, our data showed that CFl is a promising antitumor agent through kinases and transcription factor induction, both of which are required to activate TRAIL receptors. Colon inflammation induced by LPS was inhibited by CFl hydrolate.

Skala SL, Dhanasekaran SM, Mehra R
Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome (HLRCC): A Contemporary Review and Practical Discussion of the Differential Diagnosis for HLRCC-Associated Renal Cell Carcinoma.
Arch Pathol Lab Med. 2018; 142(10):1202-1215 [PubMed] Related Publications

Kim SL, Min IS, Park YR, et al.
Lipocalin 2 inversely regulates TRAIL sensitivity through p38 MAPK-mediated DR5 regulation in colorectal cancer.
Int J Oncol. 2018; 53(6):2789-2799 [PubMed] Related Publications
TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis through death receptors (DRs)4 and/or 5 expressed on the cell surface. Multiple clinical trials are underway to evaluate the antitumor activity of recombinant human TRAIL and agonistic antibodies to DR4 or DR5. However, their therapeutic potential is limited by the high frequency of cancer resistance. In this study, we provide evidence demonstrating the role of lipocalin 2 (LCN2) in the TRAIL-mediated apoptosis of human colorectal cancer (CRC). By analyzing the mRNA expression data of 71 CRC tissues from patients, we found that DR5 was preferentially expressed in CRC tissues with a low LCN2 expression level compared to tissues with a high LCN2 expression level. Moreover, we analyzed the association between DR5 and LCN2 expression and this analysis revealed that DR5 expression in CRC tended to be inversely associated with LCN2 expression. By contrast, no association was found between the DR4 and LCN2 expression levels. The expression patterns of LCN2 in human CRC cell lines also exhibited an inverse association with DR5 expression. The knockdown of LCN2 by siRNA in the TRAIL‑resistant CRC cells expressing high levels of LCN2 led to a significant increase in TRAIL-induced apoptosis through the upregulation of DR5 protein and mRNA expression. The mechanism through which LCN2 silencing sensitized the CRC cells to TRAIL was dependent on the extrinsic pathway of apoptosis. In addition, we identified that the knockdown of LCN2 enhanced the sensitivity of the cells to TRAIL through the p38 MAPK/CHOP-dependent upregulation of DR5. Taken together, the findings of this study suggest that LCN2 is responsible for TRAIL sensitivity and LCN2 may thus prove to be a promising target protein in DR-targeted CRC therapy.

Qadir F, Aziz MA, Sari CP, et al.
Transcriptome reprogramming by cancer exosomes: identification of novel molecular targets in matrix and immune modulation.
Mol Cancer. 2018; 17(1):97 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Exosomes are extracellular vesicles released by almost all cell types, including cancer cells, into bodily fluids such as saliva, plasma, breast milk, semen, urine, cerebrospinal fluid, amniotic fluid, synovial fluid and sputum. Their key function being intercellular communication with both neighbouring as well as distant cells. Cancer exosomes have been shown to regulate organ-specific metastasis. However, little is known about the functional differences and molecular consequences of normal cells responding to exosomes derived from normal cells compared to those derived from cancer cells.
METHODS: Here, we characterised and compared the transcriptome profiles of primary human normal oral keratinocytes (HNOK) in response to exosomes isolated from either primary HNOK or head and neck squamous cell carcinoma (HNSCC) cell lines.
RESULTS: In recipient HNOK cells, we found that regardless of normal or cancer derived, exosomes altered molecular programmes involved in matrix modulation (MMP9), cytoskeletal remodelling (TUBB6, FEZ1, CCT6A), viral/dsRNA-induced interferon (OAS1, IFI6), anti-inflammatory (TSC22D3), deubiquitin (OTUD1), lipid metabolism and membrane trafficking (BBOX1, LRP11, RAB6A). Interestingly, cancer exosomes, but not normal exosomes, modulated expression of matrix remodelling (EFEMP1, DDK3, SPARC), cell cycle (EEF2K), membrane remodelling (LAMP2, SRPX), differentiation (SPRR2E), apoptosis (CTSC), transcription/translation (KLF6, PUS7). We have also identified CEP55 as a potential cancer exosomal marker.
CONCLUSIONS: In conclusion, both normal and cancer exosomes modulated unique gene expression pathways in normal recipient cells. Cancer cells may exploit exosomes to confer transcriptome reprogramming that leads to cancer-associated pathologies such as angiogenesis, immune evasion/modulation, cell fate alteration and metastasis. Molecular pathways and biomarkers identified in this study may be clinically exploitable for developing novel liquid-biopsy based diagnostics and immunotherapies.

Luk PP, Selinger CI, Mahar A, Cooper WA
Biomarkers for ALK and ROS1 in Lung Cancer: Immunohistochemistry and Fluorescent In Situ Hybridization.
Arch Pathol Lab Med. 2018; 142(8):922-928 [PubMed] Related Publications
CONTEXT: - A small proportion of non-small cell lung cancers harbor rearrangements of ALK or ROS1 genes, and these tumors are sensitive to targeted tyrosine kinase inhibitors. It is crucial for pathologists to accurately identify tumors with these genetic alterations to enable patients to access optimal treatments and avoid unnecessary side effects of less effective agents. Although a number of different techniques can be used to identify ALK- and ROS1-rearranged lung cancers, immunohistochemistry and fluorescence in situ hybridization are the mainstays.
OBJECTIVE: - To review the role of immunohistochemistry in assessment of ALK and ROS1 rearrangements in lung cancer, focusing on practical issues in comparison with other modalities such as fluorescence in situ hybridization.
DATA SOURCES: - This manuscript reviews the current literature on ALK and ROS1 detection using immunohistochemistry and fluorescence in situ hybridization as well as current recommendations.
CONCLUSIONS: - Although fluorescence in situ hybridization remains the gold standard for detecting ALK and ROS1 rearrangement in non-small cell lung cancer, immunohistochemistry plays an important role and can be an effective screening method for detection of these genetic alterations, or a diagnostic test in the setting of ALK.

von Gruenigen VE, Huang HQ, Cella D, et al.
Quality of life, symptoms and care needs in patients with persistent or recurrent platinum-resistant ovarian cancer: An NRG Oncology/Gynecologic Oncology Group study.
Gynecol Oncol. 2018; 150(1):119-126 [PubMed] Related Publications
OBJECTIVES: The goals of treating recurrent platinum-resistant ovarian cancer are palliative, aimed at reducing symptoms and improving progression free survival. A prospective trial was conducted to determine the prevalence and severity of symptoms, and associated care needs.
METHODS: Eligible women included those with persistent or recurrent platinum-resistant ovarian cancer with an estimated life expectancy of at least 6 months. The Needs at the End-of-Life Screening Tool (NEST), FACIT-Fatigue (FACIT-F), NCCN-FACT Ovarian Symptom Index [NFOSI-18]; Disease Related Symptoms (DRS), Treatment Side Effects (TSE), and Function/Well Being (F/WB) were collected at study entry, 3 and 6 months.
RESULTS: We enrolled 102 evaluable patients. Initiation of Do Not Resuscitate (DNR) discussions increased over time from 28% at study entry to 37% at 6 months. At study entry, the most common disease-related symptoms were fatigue (92%), worry (89%), and trouble sleeping (76%); 73% reported being "bothered by treatment side effects", which included nausea (41%) and hair loss (51%) neither of which changed over time. The most common NEST unmet needs were in the symptom dimension. The social dimension was associated with F/WB (p = 0.002) and FACIT-F (p = 0.006); symptoms were associated with DRS (p = 0.04), TSE (p = 0.03), and FACIT-F (p = 0.04); existential was not associated with any of the patient-reported symptoms; therapeutic was associated with F/WB (p = 0.02).
CONCLUSIONS: In patients nearing the end of life, there are significant associations between disease and treatment related symptoms and unmet patient needs, which do not change substantially over time. Careful exploration of specific end-of-life care needs can improve patient-centered care and QOL.

Negulescu AM, Mehlen P
Dependence receptors - the dark side awakens.
FEBS J. 2018; 285(21):3909-3924 [PubMed] Related Publications
Transmembrane receptors are usually seen as on and off switches: when the specific ligand is bound, the receptor is on and transduces a downstream signal, whereas when the ligand is absent, the receptor is off. Over the last two decades several reports have argued for an alternative view where some receptors, depending on the context, will be active both in the presence and in the absence of ligand, being sort of on

Johnson DN, Furtado LV, Long BC, et al.
Noninvasive Follicular Thyroid Neoplasms With Papillary-like Nuclear Features Are Genetically and Biologically Similar to Adenomatous Nodules and Distinct From Papillary Thyroid Carcinomas With Extensive Follicular Growth.
Arch Pathol Lab Med. 2018; 142(7):838-850 [PubMed] Related Publications
CONTEXT: - Proposed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs), formerly noninvasive encapsulated papillary carcinoma, follicular variant (PTC-FV), is an indolent tumor with follicular growth and frequent RAS mutations.
OBJECTIVE: - To detect histologic and molecular differences separating NIFTP from follicular adenomas (FAs) and invasive carcinomas, particularly papillary carcinomas with extensive follicular growth (PTC-EFGs) and invasive encapsulated PTC-FV (IE-PTC-FV).
DESIGN: - Sixty-one tumors were reviewed histologically and reclassified into 32 NIFTPs (52%), 4 IE-PTC-FVs (7%), 14 PTC-EFGs (23%), and 11 FAs (18%). Next-generation sequencing for mutations in 50 genes was performed. Clinical outcomes were recorded.
RESULTS: - The NIFTPs and FAs were well circumscribed and unencapsulated. The FAs had bland nuclei, whereas the NIFTPs showed at least 2 of 3 (67%; sufficient) nuclear features (enlargement, irregular contours, chromatin clearing). The IE-PTC-FVs had follicular growth, sufficient nuclear features, and extensive capsular invasion. The PTC-EFGs had a median of 5% papillae with intrathyroidal invasion (broad-based, sclerotic, or small follicle growth patterns); intranuclear pseudoinclusions were present only in PTC-EFGs (9 of 14; 64%). Mutations included RAS in 20 of the 32 NIFTPs (62%), 4 of the 11 FAs (36%), and 3 of the 4 IE-PTC-FVs (75%); BRAF K601E in 1 NIFTP (3%); BRAF V600E in 5 PTC-EFGs (36%). No NIFTPs or FAs recurred or metastasized. All 4 IE-PTC-FVs (100%) had hematogenous metastasis. Two PTC-EFGs (14%) had lymphatic metastasis.
CONCLUSIONS: - The morphologic similarity and RAS mutations in FAs, NIFTPs, and IE-PTC-FVs supports the genetic similarity of those follicular neoplasms in contrast to the unique presence of BRAF V600E mutations in PTC-EFGs. Using strict diagnostic criteria supported by molecular testing, tumors with extensive follicular growth can be classified into follicular type or RAS-like (FA, NIFTP, IE-PTC-FV) versus papillary type or BRAF V600E-like (PTC-EFG).

de Biase D, Visani M, Acquaviva G, et al.
The Role of Next-Generation Sequencing in the Cytologic Diagnosis of Pancreatic Lesions.
Arch Pathol Lab Med. 2018; 142(4):458-464 [PubMed] Related Publications
CONTEXT: - Integration of the analysis of genetic markers with endoscopic ultrasound-guided fine-needle aspiration and cytologic evaluation has increased the accuracy of the preoperative diagnosis of pancreatic lesions. The application of high-throughput gene panel analysis using next-generation sequencing platforms is now offering a great opportunity for further improvements.
OBJECTIVE: - To review the application of next-generation sequencing to the preoperative diagnosis of pancreatic lesions.
DATA SOURCES: - For data acquisition, a PubMed search using the terms next-generation sequencing, pancreas, pancreatic lesions, pancreatic tumors, and EUS-FNA was performed covering the years 2000-2017.
CONCLUSIONS: - KRAS remains the gene most widely studied for preoperative single-gene tests. Next-generation sequencing reliably allows analysis of multiple gene markers starting from limited amounts of DNA. The study of multigene panels has become a very attractive option for the management and preoperative risk stratification of patients with pancreatic cancer.

Teixidó C, Giménez-Capitán A, Molina-Vila MÁ, et al.
RNA Analysis as a Tool to Determine Clinically Relevant Gene Fusions and Splice Variants.
Arch Pathol Lab Med. 2018; 142(4):474-479 [PubMed] Related Publications
CONTEXT: - Technologic advances have contributed to the increasing relevance of RNA analysis in clinical oncology practice. The different genetic aberrations that can be screened with RNA include gene fusions and splice variants. Validated methods of identifying these alterations include fluorescence in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction, and next-generation sequencing, which can provide physicians valuable information on disease and treatment of cancer patients.
OBJECTIVE: - To discuss the standard techniques available and new approaches for the identification of gene fusions and splice variants in cancer, focusing on RNA analysis and how analytic methods have evolved in both tissue and liquid biopsies.
DATA SOURCES: - This is a narrative review based on PubMed searches and the authors' own experiences.
CONCLUSIONS: - Reliable RNA-based testing in tissue and liquid biopsies can inform the diagnostic process and guide physicians toward the best treatment options. Next-generation sequencing methodologies permit simultaneous assessment of molecular alterations and increase the number of treatment options available for cancer patients.

Kizy S, Huang JL, Marmor S, et al.
Distribution of 21-Gene Recurrence Scores Among Breast Cancer Histologic Subtypes.
Arch Pathol Lab Med. 2018; 142(6):735-741 [PubMed] Related Publications
CONTEXT: - The 21-gene recurrence score (RS) provides a probability of distant recurrence for estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers. The utility of RS for rarer histologic subtypes of breast cancer is uncertain.
OBJECTIVE: - To determine the distribution of RS among various histologic subtypes using a population database.
DESIGN: - Women between the ages of 18 and 75 with estrogen receptor-positive, HER2-negative breast cancer and known RS results were identified using the Surveillance, Epidemiology, and End Results database. Recurrence scores were categorized into risk groups using both traditional and Trial Assigning Individualized Options for Treatment cutoffs. Multivariable logistic regression was used to determine factors associated with high-risk RS.
RESULTS: - We identified 45 618 patients with stage I to III, estrogen receptor-positive, HER2-negative breast cancer who had RS available. Overall, 3087 (7%) and 6337 (14%) of cancers were classified as high risk based on traditional and Trial Assigning Individualized Options for Treatment RS cutoffs, respectively. The proportion of high-risk RS ranged from 1% (tubular, 2 of 225) to 68% (medullary, 13 of 19) and 4% (tubular, 10 of 225) to 79% (medullary, 15 of 19) for traditional and Trial Assigning Individualized Options for Treatment cutoffs, respectively. Based on multivariable logistic regression (excluding medullary), subtypes other than invasive ductal carcinoma and papillary carcinoma were significantly associated with lower RS. The strongest predictors of a high-risk RS were higher tumor grade and negative progesterone receptor status.
CONCLUSIONS: - We identified distinct distributions of RS among different histologic subtypes of breast cancer. Excluding medullary carcinoma, histologic subtypes other than invasive ductal carcinoma and papillary carcinoma all predict lower RS.

Rinaldetti S, Pfirrmann M, Manz K, et al.
Effect of ABCG2, OCT1, and ABCB1 (MDR1) Gene Expression on Treatment-Free Remission in a EURO-SKI Subtrial.
Clin Lymphoma Myeloma Leuk. 2018; 18(4):266-271 [PubMed] Related Publications
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated.
MATERIALS AND METHODS: RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial. Plasmid standards were designed including subgenic inserts of OCT1, ABCG2, and ABCB1 together with GUSB as reference gene. For expression analyses, quantitative real-time polymerase chain reaction was used. Multiple Cox regression analysis was performed. In addition, gene expression cutoffs for patient risk stratification were investigated.
RESULTS: The TFR rate of 132 patients, 12 months after TKI discontinuation, was 54% (95% confidence interval [CI], 46%-62%). ABCG2 expression (‰) was retained as the only significant variable (P = .02; hazard ratio, 1.04; 95% CI, 1.01-1.07) in multiple Cox regression analysis. Only for the ABCG2 efflux transporter, a significant cutoff was found (P = .04). Patients with an ABCG2/GUSB transcript level >4.5‰ (n = 93) showed a 12-month TFR rate of 47% (95% CI, 37%-57%), whereas patients with low ABCG2 expression (≤4.5‰; n = 39) had a 12-month TFR rate of 72% (95% CI, 55%-82%).
CONCLUSION: In this study, we investigated the effect of pharmacogenetics in the context of a CML treatment discontinuation trial. The transcript levels of the efflux transporter ABCG2 predicted TFR after TKI discontinuation.

Lozano MD, Echeveste JI, Abengozar M, et al.
Cytology Smears in the Era of Molecular Biomarkers in Non-Small Cell Lung Cancer: Doing More With Less.
Arch Pathol Lab Med. 2018; 142(3):291-298 [PubMed] Related Publications
CONTEXT: - The rapid advances in targeted therapies in non-small cell lung cancer (NSCLC) make the optimization and implementation of cytology specimens for molecular testing a priority. Up to 70% of patients with NSCLC are diagnosed at advanced stages and tissue biopsies often cannot be taken. Although cytology samples provide high-quality material for molecular testing, molecular cytopathology is not yet well known or widely used.
OBJECTIVE: - To report the many advances in molecular cytopathology and the suitability and utility of cytology samples in molecular and genetic testing of NSCLC.
DATA SOURCES: - Data sources comprised published peer-reviewed literature and personal experience of the authors.
CONCLUSIONS: - Molecular testing can be performed on cytologic specimens, especially on direct smears. Rapid on-site evaluation by cytopathologists has improved the adequacy and the management of cytology samples for molecular testing. Mutational profiling of NSCLC using next-generation sequencing can be performed on cytology samples from very small amounts of DNA. Fluorescence in situ hybridization assays on cytology specimens, including stained direct smear, offer some distinct advantages over their histologic counterpart, and are used to detect ALK and ROS1 rearrangements in NSCLC. Cytology specimens allow assessment of the entire tumor cell nucleus, avoiding signal loss from truncation artifacts. The use of cytology samples for assessing programmed death ligand-1 protein expression is currently being developed. Protocols for bisulfite conversion and DNA droplet digital polymerase chain reaction assays have been optimized for cytology smear to investigate aberrant DNA methylation of several NSCLC-related genes.

Pai T, Shet T, Patil A, et al.
Utility of Alternate, Noncentromeric Chromosome 17 Reference Probe for Human Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization Testing in Breast Cancer Cases.
Arch Pathol Lab Med. 2018; 142(5):626-633 [PubMed] Related Publications
Context PathVysion-a US Food and Drug Administration-approved dual-probe human epidermal growth factor receptor ( HER2) fluorescence in situ hybridization (FISH) assay-provides the HER2: CEP17 ratio, a centromeric enumeration probe ratio for determining HER2 status in breast cancers. However, pericentromeric amplifications might then skew the HER2: CEP17 ratio, underestimating the HER2 status, which calls into question the use of CEP17 as the reference probe. Objective To analyze the utility of a noncentromeric chromosome 17 reference locus ( D17S122) to assess HER2 gene status in cases showing "nonclassical" FISH patterns with the CEP17 probe. Design The HER2 status of breast cancers accessioned in the years 2015-2017, displaying "nonclassical" or "equivocal" results by the PathVysion (Abbott Molecular Inc, Des Plaines, Illinois) HER2 DNA Probe Kit were reflex tested using an alternate FISH probe (ZytoLight SPEC/D17S122, ZytoVision, Bremerhaven, Germany) and interpreted with American Society of Clinical Oncology/College of American Pathologists 2013 guidelines. Results Of 37 cases, 17 were FISH equivocal. With the alternate D17S122 probe, 13 (76.4%) were reclassified as amplified, 3 (17.6%) as nonamplified, and a single case retained an equivocal result. Of the 17 cases with a chromosome 17 polysomy pattern, disomy, polysomy, and monosomy patterns were seen with 14 cases, 2 cases, and 1 case, respectively. Within the 17 cases with polysomy pattern, 3 (17.6%) demonstrated an unusual colocalization pattern of HER2 and CEP17, which was not observed with the alternate probe. Conclusions The denominator-stable alternate probe is a useful adjunct in the diagnostic armamentarium to analyze HER2 status in cases with FISH equivocal and complex patterns.

Alì G, Bruno R, Savino M, et al.
Analysis of Fusion Genes by NanoString System: A Role in Lung Cytology?
Arch Pathol Lab Med. 2018; 142(4):480-489 [PubMed] Related Publications
CONTEXT: - Patients with non-small cell lung cancer harboring ALK receptor tyrosine kinase ( ALK), ROS proto-oncogene 1 ( ROS1), and ret proto-oncogene ( RET) gene rearrangements can benefit from specific kinase inhibitors. Detection of fusion genes is critical for determining the best treatment. Assessing rearrangements in non-small cell lung cancer remains challenging, particularly for lung cytology.
OBJECTIVE: - To examine the possible application of the multiplex, transcript-based NanoString system (NanoString Technologies, Seattle, Washington) in the evaluation of fusion genes in lung adenocarcinoma samples.
DATA SOURCES: - This study is a narrative literature review. Studies about NanoString, gene fusions, and lung adenocarcinoma were collected from PubMed (National Center for Biotechnology Information, Bethesda, Maryland). We found 7 articles about the application of the NanoString system to detect fusion genes on formalin-fixed, paraffin-embedded tumor tissues and one article evaluating the adequacy of lung cytologic specimens for NanoString gene expression analysis.
CONCLUSIONS: - To maximize the yield of molecular tests on small lung biopsies, the NanoString nCounter system has been suggested to detect fusion genes. NanoString fusion gene assays have been successfully applied on formalin-fixed, paraffin-embedded tissues. Although there are only a few studies available, the application of NanoString assays may also be feasible in lung cytology. According to available data, the NanoString system could strengthen the routine molecular characterization of lung adenocarcinoma.

Lindeman NI, Cagle PT, Aisner DL, et al.
Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
Arch Pathol Lab Med. 2018; 142(3):321-346 [PubMed] Related Publications
CONTEXT: - In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing.
OBJECTIVE: - To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update.
DESIGN: - The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations.
RESULTS: - Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline.
CONCLUSIONS: - The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes ( ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to "rule in" targetable mutations when tissue is limited or hard to obtain.

Mehrad M, Roy S, Bittar HT, Dacic S
Next-Generation Sequencing Approach to Non-Small Cell Lung Carcinoma Yields More Actionable Alterations.
Arch Pathol Lab Med. 2018; 142(3):353-357 [PubMed] Related Publications
CONTEXT: - Different testing algorithms and platforms for EGFR mutations and ALK rearrangements in advanced-stage lung adenocarcinoma exist. The multistep approach with single-gene assays has been challenged by more efficient next-generation sequencing (NGS) of a large number of gene alterations. The main criticism of the NGS approach is the detection of genomic alterations of uncertain significance.
OBJECTIVE: - To determine the best testing algorithm for patients with lung cancer in our clinical practice.
DESIGN: - Two testing approaches for metastatic lung adenocarcinoma were offered between 2012-2015. One approach was reflex testing for an 8-gene panel composed of DNA Sanger sequencing for EGFR, KRAS, PIK3CA, and BRAF and fluorescence in situ hybridization for ALK, ROS1, MET, and RET. At the oncologist's request, a subset of tumors tested by the 8-gene panel was subjected to a 50-gene Ion AmpliSeq Cancer Panel.
RESULTS: - Of 1200 non-small cell lung carcinomas (NSCLCs), 57 including 46 adenocarcinomas and NSCLCs, not otherwise specified; 7 squamous cell carcinomas (SCCs); and 4 large cell neuroendocrine carcinomas (LCNECs) were subjected to Ion AmpliSeq Cancer Panel. Ion AmpliSeq Cancer Panel detected 9 potentially actionable variants in 29 adenocarcinomas that were wild type by the 8-gene panel testing (9 of 29, 31.0%) in the following genes: ERBB2 (3 of 29, 10.3%), STK11 (2 of 29, 6.8%), PTEN (2 of 29, 6.8%), FBXW7 (1 of 29, 3.4%), and BRAF G469A (1 of 29, 3.4%). Four SCCs and 2 LCNECs showed investigational genomic alterations.
CONCLUSIONS: - The NGS approach would result in the identification of a significant number of actionable gene alterations, increasing the therapeutic options for patients with advanced NSCLCs.

Kitao H, Iimori M, Kataoka Y, et al.
DNA replication stress and cancer chemotherapy.
Cancer Sci. 2018; 109(2):264-271 [PubMed] Free Access to Full Article Related Publications
DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). When we consider therapeutic approaches for tumors, it is important to exploit the differences in DRS between tumor and normal cells. In this review, we introduce the current understanding of DRS in tumors and discuss the underlying mechanism of cancer therapy from the aspect of DRS.

Lucas D, O'Leary HA, Ebert BL, et al.
Utility of CRISPR/Cas9 systems in hematology research.
Exp Hematol. 2017; 54:1-3 [PubMed] Related Publications
Since the end of the 20th century, novel approaches have emerged to manipulate experimental models of hematological disorders so that they more accurately mirror what is observed in the clinical setting. Despite these technological advances, the characterization of crucial genes for benign or malignant hematological disorders remains challenging, given the dynamic nature of the hematopoietic system and the genetic heterogeneity of these disorders. To overcome this limitation, genome-editing technologies have been developed to manipulate the genome specifically via deletion, insertion, or modification of targeted loci. These technologies have progressed swiftly, allowing their common use to investigate genetic function in experimental hematology. Among them, homologous-recombination-mediated targeting technologies have facilitated the manipulation of specific loci by generating knock-out and knock-in models. Despite promoting significant advances in our understanding of the molecular mechanisms involved in hematology, these inefficient, time-consuming, and labor-intensive approaches did not permit the development of cellular or animal models, recapitulating the complexity of hematological disorders. On October 26, 2016, Drs. Ben Ebert and Chad Cowan shared their knowledge of and experience with the utilization of CRISPR for models of myeloid malignancy, disease, and novel therapeutics in an International Society for Experimental Hematology webinar titled "Utility of CRISPR/Cas9 Systems in Hematology Research." Here, we provide an overview of the topics they covered, including their insights into the novel applications of the technique and its strengths and limitations.

Thomas M, Sukhai MA, Zhang T, et al.
Integration of Technical, Bioinformatic, and Variant Assessment Approaches in the Validation of a Targeted Next-Generation Sequencing Panel for Myeloid Malignancies.
Arch Pathol Lab Med. 2017; 141(6):759-775 [PubMed] Related Publications
CONTEXT: - Detection of variants in hematologic malignancies is increasingly important because of a growing number of variants impacting diagnosis, prognosis, and treatment response, and as potential therapeutic targets. The use of next-generation sequencing technologies to detect variants in hematologic malignancies in a clinical diagnostic laboratory setting allows for efficient identification of routinely tested markers in multiple genes simultaneously, as well as the identification of novel and rare variants in other clinically relevant genes.
OBJECTIVE: - To apply a systematic approach to evaluate and validate a commercially available next-generation sequencing panel (TruSight Myeloid Sequencing Panel, Illumina, San Diego, California) targeting 54 genes. In this manuscript, we focused on the parameters that were used to evaluate assay performance characteristics.
DATA SOURCES: - Analytical validation was performed using samples containing known variants that had been identified previously. Cases were selected from different disease types, with variants in a range of genes. Panel performance characteristics were assessed and genomic regions requiring additional analysis or wet-bench approaches identified.
CONCLUSIONS: - We validated the performance characteristics of a myeloid next-generation sequencing panel for detection of variants. The TruSight Myeloid Sequencing Panel covers more than 95% of target regions with depth greater than 500×. However, because of unique variant types such as large insertions or deletions or genomic regions of high GC content, variants in CEBPA, FLT3, and CALR required supplementation with non-next-generation sequencing assays or with informatics approaches to address deficiencies in performance. The use of multiple bioinformatics approaches (2 variant callers and informatics scripts) allows for maximizing calling of true positives, while identifying limitations in using either method alone.

Garcia EP, Minkovsky A, Jia Y, et al.
Validation of OncoPanel: A Targeted Next-Generation Sequencing Assay for the Detection of Somatic Variants in Cancer.
Arch Pathol Lab Med. 2017; 141(6):751-758 [PubMed] Related Publications
CONTEXT: - The analysis of somatic mutations across multiple genes in cancer specimens may be used to aid clinical decision making. The analytical validation of targeted next-generation sequencing panels is important to assess accuracy and limitations.
OBJECTIVE: - To report the development and validation of OncoPanel, a custom targeted next-generation sequencing assay for cancer.
DESIGN: - OncoPanel was designed for the detection of single-nucleotide variants, insertions and deletions, copy number alterations, and structural variants across 282 genes with evidence as drivers of cancer biology. We implemented a validation strategy using formalin-fixed, paraffin-embedded, fresh or frozen samples compared with results obtained by clinically validated orthogonal technologies.
RESULTS: - OncoPanel achieved 98% sensitivity and 100% specificity for the detection of single-nucleotide variants, and 84% sensitivity and 100% specificity for the detection of insertions and deletions compared with single-gene assays and mass spectrometry-based genotyping. Copy number detection achieved 86% sensitivity and 98% specificity compared with array comparative genomic hybridization. The sensitivity of structural variant detection was 74% compared with karyotype, fluorescence in situ hybridization, and polymerase chain reaction. Sensitivity was affected by inconsistency in the detection of FLT3 and NPM1 alterations and IGH rearrangements due to design limitations. Limit of detection studies demonstrated 98.4% concordance across triplicate runs for variants with allele fraction greater than 0.1 and at least 50× coverage.
CONCLUSIONS: - The analytical validation of OncoPanel demonstrates the ability of targeted next-generation sequencing to detect multiple types of genetic alterations across a panel of genes implicated in cancer biology.

Wang X, Gao Y, Wang B, et al.
Analytic and Clinical Validation of an Ultrasensitive, Quantitative Polymerase Chain Reaction Assay for EGFR Mutation Analysis With Circulating Tumor DNA.
Arch Pathol Lab Med. 2017; 141(7):978-984 [PubMed] Related Publications
CONTEXT: - The mutation analysis of epidermal growth factor receptor (EGFR) has become a common test to guide therapeutic decision making for lung cancer. Molecular testing with circulating tumor DNA in plasma allows diagnosis of mutations when tumor tissue is not available as well as monitoring treatment response with repeat biopsies.
OBJECTIVES: - To develop a timely and cost-effective assay that can accurately detect EGFR mutations in circulating tumor DNA and to evaluate the analytic and clinical performance of the assay.
DESIGN: - Analytic assessment was conducted with a set of reference materials carrying classic EGFR mutations. A recently developed Poisson distribution-based approach was employed to understand the assay sensitivity. Clinical evaluation was performed with 224 pairs of plasma and matched tissues from patients with stage I to IV disease. EGFR mutation rates of 390 consecutive plasma samples processed in the central service laboratory were compared with previously reported prevalence in an Asian population.
RESULTS: - Our results suggested that limit of detection for the EGFR quantitative polymerase chain reaction assay was 10 mutation copies, and the lowest detectable copy numbers could be extended to a single-digit level. The clinical sensitivity was 53.3% for all stages combined and 81.4% for late stages, with a high specificity of 100%. Clinical observations showed an overall positive finding rate of 32.5% and 41.4% for stage IV disease, which is consistent with previously reported EGFR mutation prevalence in an Asian population.
CONCLUSIONS: - Our results supported the clinical utility of the ultrasensitive, quantitative polymerase chain reaction assay for EGFR mutation analysis with circulating tumor DNA.

Kong X, Luo J, Xu T, et al.
Plumbagin enhances TRAIL-induced apoptosis of human leukemic Kasumi‑1 cells through upregulation of TRAIL death receptor expression, activation of caspase-8 and inhibition of cFLIP.
Oncol Rep. 2017; 37(6):3423-3432 [PubMed] Related Publications
Although the patients with t(8;21) acute myeloid leukemia (AML) have a favorable prognosis compared with other non-acute promyelocytic leukemia AML patients, only ~50% patients with this relatively favorable subtype can survive for 5 years and refractory/relapse is common in clinical practice. So it is necessary to find novel agents to treat this type of AML. In this study, the effects and the mechanisms of plumbagin and recombinant soluble tumor necrosis factor‑α-related apoptosis-inducing ligand (rsTRAIL) on leukemic Kasumi‑1 cells were primarily investigated. Plumbagin and/or rsTRAIL could significantly inhibit the growth of Kasumi‑1 cells and induce apoptosis in vitro and in vivo. Plumbagin enhanced TRAIL-induced apoptosis of Kasumi‑1 cells in association with mitochondria damage, caspase activation, upregulation of death receptors (DRs) and decreased cFLIP expression. The effects of plumbagin on the expression of DR5, Bax and cFLIP could be partially abolished by the reactive oxygen species (ROS) scavenger NAC. Glutathione (GSH) depletion by plumbagin increased the production of ROS. In vivo, there was no obvious toxic pathologic change in the heart, liver and kidney tissues in any of the groups. Comparing with the control mice, a significantly increased number of apoptotic cells were observed in the combined treated mice by flow cytometry. Plumbagin also increased the expression of DR4 and DR5 in cells of xenograft tumors. Collectively, our results suggest that both plumbagin and rsTRAIL could be used as a single agent or synergistical agents to induce apoptosis of leukemic Kasumi‑1 cells in vitro and in vivo.

Kardosh M, Bar-Tal Y, Barnoy S
The Relationship Between Body Image, Gender, Subjective Norms, and the Decision to Undergo Preventive Mastectomy Among Arab and Jewish BRCA Carriers.
Cancer Nurs. 2018 May/Jun; 41(3):255-262 [PubMed] Related Publications
BACKGROUND: Carriers for a mutation in BRCA1/2 genes have a high, lifelong risk for developing breast cancer. Preventive mastectomy is considered an effective risk reduction surgery. Many factors might affect the decision to undergo preventive mastectomy, including culture, perceived body image after mastectomy and important others opinion.
OBJECTIVE: The aim of this study is to evaluate BRCA mutation carriers' decision to undergo preventive mastectomy and the relationship between culture, gender, body image, and the decision.
METHODS: The study was a cross-sectional design where Arab and Jewish men and women were requested to imagine that they were/their spouse was a BRCA mutation carrier. The sample consisted of 200 participants, 101 Arab and 99 Jews, included 101 women and 99 men.
RESULTS: The results show a high intention to undergo preventive mastectomy. Being Arab and having a more positive perception of body image after the surgery were connected to more intention to undergo the surgery. Also, those who intended to choose the surgery considered more the opinions of important others.
CONCLUSIONS: The results point to the importance of partners' involvement in the decision to undergo preventive mastectomy. Also, important others (relatives, friends, and health caregivers) have an impact on the decision.
IMPLICATIONS FOR PRACTICE: Nurses need to consider cultural aspects of patients considering a decision about whether to undergo preventive mastectomy. Understanding the important others who might influence the decision and including them in the decision process are both essential.

Harrison G, Sosa JA, Jiang X
Evaluation of the Afirma Gene Expression Classifier in Repeat Indeterminate Thyroid Nodules.
Arch Pathol Lab Med. 2017; 141(7):985-989 [PubMed] Related Publications
CONTEXT: - Molecular testing in indeterminate thyroid nodules is a rapidly evolving field with variable reported outcomes.
OBJECTIVE: - To report our experience at a tertiary thyroid referral center with the Afirma Gene Expression Classifier (Veracyte, San Francisco, California) in repeat fine-needle aspirations of thyroid nodules with a previous indeterminate cytologic result.
DESIGN: - Results of cytopathology and the Afirma test were collected from August 2013 to March 2015, as were diagnoses from surgical resection when performed.
RESULTS: - One hundred and fifteen thyroid nodules were evaluated by Afirma. The fine-needle aspiration diagnostic categories for these nodules were 100 (87%) Bethesda III, 10 (9%) Bethesda IV, 3 (2%) Bethesda II, 1 (1%) Bethesda V, and 1 (1%) Bethesda I. Afirma results for 52 of the nodules (45%) were benign, 57 (50%) were suspicious, and 6 (5%) specimens yielded no result because of low messenger RNA content. Three of the benign nodules (6%) were treated surgically, and all were benign on final surgical pathology. Forty-six (81%) of the suspicious nodules were treated surgically; final surgical pathology revealed 30 (65%) were benign and 16 (35%) malignant, yielding a positive predictive value of 35%.
CONCLUSIONS: - In our experience, 50% of the indeterminate nodules were classified as suspicious by Afirma, with a 35% rate of malignancy in these nodules at surgical resection, in comparison with a historical rate of malignancy at our institution of 11% for Bethesda III nodules and 23% for Bethesda IV. Our use of Afirma is consistent with prior reports in that it has a low positive predictive value in indeterminate thyroid nodules.

Guan J, Lim KS, Mekhail T, Chang CC
Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers.
Arch Pathol Lab Med. 2017; 141(6):851-861 [PubMed] Related Publications
CONTEXT: - Immune checkpoint pathways, including programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, which are important in mediating self-tolerance and controlling self-damage, can sometimes be manipulated by cancer cells to evade immune surveillance. Recent clinical trials further demonstrate the efficacy of PD-1/PD-L1-targeted therapy in various cancers and reveal a new era of cancer immunotherapy.
OBJECTIVE: - To review the mechanism of the PD-1/PD-L1 signaling pathway, the regulation of this pathway, PD-1/PD-L1 as a predictive and/or prognostic marker in various cancers, and strategies of measuring PD-L1 expression.
DATA SOURCES: - Representative medical literature regarding PD-L1 expression in various cancers, including the preliminary results of the Blue Proposal, which compares different immunohistochemical stains for PD-L1 reported in the recent American Association of Cancer Research (AACR) Annual Meeting (April 16-20, 2016).
CONCLUSION: - Either PD-1/PD-L1-targeted therapy alone or in combination with other treatment modalities provides benefit for patients with advanced cancers. Because of the complexity of cancer immunity, we still do not have a reliable biomarker to predict the response of PD-1/PD-L1-targeted therapy. Future studies, including methods beyond immunohistochemical stains, are needed to develop reliable biomarker/biomarkers for pathology laboratories to aid in selecting patients who will benefit most from PD-1/PD-L1-targeted therapy.

Hanley KZ, Birdsong GG, Mosunjac MB
Recent Developments in Surgical Pathology of the Uterine Corpus.
Arch Pathol Lab Med. 2017; 141(4):528-541 [PubMed] Related Publications
There have been several updates recently on the classification of uterine tumors. Endometrial carcinomas have traditionally been divided into 2 types, but some are difficult to classify and do not fit readily into either of the currently recognized categories. The Cancer Genome Atlas Research Network has recently defined 4 new categories of endometrial cancer on the basis of mutational spectra, copy number alteration, and microsatellite instability, which might provide independent prognostic information beyond established risk factors. The Society of Gynecologic Oncology, moreover, now recommends systematic screening of every patient with endometrial cancer for Lynch syndrome. The new definition of high-grade endometrial stromal sarcoma disregards the number of mitotic figures as a primary diagnostic criterion and instead specifies moderate atypia still resembling stromal origin but lacking the pleomorphism of undifferentiated uterine sarcoma; these tumors also harbor a JAZF1-SUZ12 gene rearrangement. Mitotic count, atypia, and coagulative necrosis are the main histologic criteria that define leiomyosarcoma. Determining the type of necrosis can be very challenging in patients receiving various treatment modalities for symptomatic fibroids before myomectomy, since key histologic features of ischemic-type necrosis are often absent. Ancillary stains including p16, p53, MIB-1, trichrome, and reticulin may be helpful in tumors harboring necrosis that is difficult to classify. Minimally invasive gynecologic surgeries have introduced histologic artifacts that complicate the diagnosis. It is essential to recognize these as procedure-related artifacts to avoid upstaging tumors and triggering unnecessary adjuvant treatment.

Lasota J, Kowalik A, Felisiak-Golabek A, et al.
SP174, NRAS Q61R Mutant-Specific Antibody, Cross-Reacts With KRAS Q61R Mutant Protein in Colorectal Carcinoma.
Arch Pathol Lab Med. 2017; 141(4):564-568 [PubMed] Related Publications
CONTEXT: - NRAS is a member of the RAS family oncoproteins implicated in cancer. Gain-of-function NRAS mutations were reported in a subset of colorectal cancers. These mutations occur at codons 12, 13, and 61 and are detected by molecular genetic testing. Recently, an antibody (clone SP174) became available to immunohistochemically pinpoint NRAS Q61R mutant protein. In malignant melanoma, NRAS Q61R mutant-specific immunohistochemistry was shown to be a valuable supplement to traditional genetic testing.
OBJECTIVE: - To evaluate the significance of NRAS Q61R mutant-specific immunohistochemistry in a cohort of colorectal carcinomas.
DESIGN: - A total of 1185 colorectal carcinomas were immunohistochemically evaluated with SP174 antibody. NRAS Q61R mutant-specific immunohistochemistry was validated by molecular genetic testing including Sanger sequencing, quantitative polymerase chain reaction (qPCR), and next-generation sequencing.
RESULTS: - Twelve tumors showed strong SP174 immunoreactivity. Sanger sequencing detected an identical c.182A>G substitution, causing NRAS Q61R mutation at the protein level, only in 8 SP174-positive cases. These results were confirmed by qPCR study. Subsequently, NRAS wild-type tumors with strong SP174 staining were evaluated by next-generation sequencing and revealed KRAS c.182A>G substitutions predicted to cause KRAS Q61R mutation. Review of colorectal carcinomas with known KRAS and NRAS genotype revealed that none of 62 wild-type tumors or 47 mutants other than Q61R were SP174 positive.
CONCLUSION: - SP174 immunohistochemistry allows sensitive detection of NRAS and KRAS Q61R mutants. However, molecular genetic testing is necessary to determine specifically which RAS gene is mutated.

Kim TH, Ki CS, Kim HS, et al.
Refining Dynamic Risk Stratification and Prognostic Groups for Differentiated Thyroid Cancer With TERT Promoter Mutations.
J Clin Endocrinol Metab. 2017; 102(5):1757-1764 [PubMed] Related Publications
Context: Currently, no recurrence or mortality risk systems consider molecular testing when predicting thyroid cancer outcomes.
Objective: We developed an integrative prognostic system that incorporates telomerase reverse transcription (TERT) promoter mutations into the recently proposed risk reclassification system after initial therapy [dynamic risk stratification (DRS)] to better categorize and predict outcomes.
Design: A total of 357 differentiated thyroid cancer (DTC) patients without initial distant metastasis were enrolled. Among patients with mutated TERT and wild-type, recurrence-free survival (RFS) was compared according to DRS grouping. Cox regression was used to calculate adjusted hazard ratios (AHRs) to derive AHR groups. Performance of the AHR grouping system with respect to prediction of structural recurrence and cancer-specific survival (CSS) was assessed against the current DRS system and the tumor/node/metastasis (TNM) classification.
Results: Among 357 patients, there were 90 recurrences and 15 cancer-related deaths during a median of 14 years of follow-up. Patients in higher AHR groups were at higher risk of recurrence (10-year RFS for AHR 1, 2, 3, and 4: 94.9%, 82.7%, 50.2%, and 23.1%; P < 0.001) and cancer-related death (10-year CSS: 100.0%. 98.7%, 94.2%, and 76.9%; P < 0.001). The proportions of variance explained (PVEs) for the ability of AHR and DRS grouping to predict recurrence were 22.4% and 18.5%. PVEs of AHR and TNM system to predict cancer-related deaths were 11.5% and 7.4%.
Conclusions: The AHR grouping system, a simple two-dimensional prognostic system, is as effective as DRS at predicting structural recurrence and provides clinical implication for long-term CSS in patients with nonmetastatic DTC.

Neill SG, Saxe DF, Rossi MR, et al.
Genomic Analysis in the Practice of Surgical Neuropathology: The Emory Experience.
Arch Pathol Lab Med. 2017; 141(3):355-365 [PubMed] Related Publications
The evaluation of central nervous system tumors increasingly relies on molecular genetic methods to aid in classification, offer prognostic information, and predict response to therapy. Available assays make it possible to assess genetic losses, amplifications, translocations, mutations, or the expression levels of specific gene transcripts or proteins. Current molecular diagnostics frequently use a panel-based approach and whole genome analysis, and generally rely either on DNA sequencing or on hybridization-based methodologies, such as those used in cytogenomic microarrays. In some cases, immunohistochemistry can be used as a surrogate for genetic analysis when the mutation of interest consistently results in overexpression or underexpression of a known protein product. In surgical neuropathology practice, the diagnostic workup of diffuse gliomas, medulloblastomas, low-grade circumscribed gliomas, as well as other diseases, now routinely incorporates the results of genomic studies. Here we summarize our institution's current approach to diagnostic surgical neuropathology, using these contemporary molecular diagnostic applications.

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