scholarly journals HSP110 as a Diagnostic but Not a Prognostic Biomarker in Colorectal Cancer With Microsatellite Instability

2022 ◽  
Vol 12 ◽  
Author(s):  
Gaelle Tachon ◽  
Arnaud Chong-Si-Tsaon ◽  
Thierry Lecomte ◽  
Audelaure Junca ◽  
Éric Frouin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Large Deletion ◽  
Molecular Testing ◽  
Predictive Tool ◽  
Time To Recurrence ◽  
Prognosis Marker ◽  
Crc Management ◽  
Chemotherapy Efficacy

Determination of microsatellite instability (MSI) using molecular test and deficient mismatch repair (dMMR) using immunohistochemistry (IHC) has major implications on colorectal cancer (CRC) management. The HSP110 T17 microsatellite has been reported to be more monomorphic than the common markers used for MSI determination. Large deletion of HSP110 T17 has been associated with efficacy of adjuvant chemotherapy in dMMR/MSI CRCs. The aim of this study was to evaluate the interest of HSP110 deletion/expression as a diagnostic tool of dMMR/MSI CRCs and a predictive tool of adjuvant chemotherapy efficacy. All patients with MSI CRC classified by molecular testing were included in this multicenter prospective cohort (n = 381). IHC of the 4 MMR proteins was carried out. HSP110 expression was carried out by IHC (n = 343), and the size of HSP110 T17 deletion was determined by PCR (n = 327). In the 293 MSI CRCs with both tests, a strong correlation was found between the expression of HSP110 protein and the size of HSP110 T17 deletion. Only 5.8% of MSI CRCs had no HSP110 T17 deletion (n = 19/327). HSP110 T17 deletion helped to re-classify 4 of the 9 pMMR/MSI discordance cases as pMMR/MSS cases. We did not observe any correlation between HSP110 expression or HSP110 T17 deletion size with time to recurrence in patients with stage II and III CRC, treated with or without adjuvant chemotherapy. HSP110 is neither a robust prognosis marker nor a predictor tool of adjuvant chemotherapy efficacy in dMMR/MSI CRC. However, HSP110 T17 is an interesting marker, which may be combined with the other pentaplex markers to identify discordant cases between MMR IHC and MSI.

TUMOUR PATHOLOGY PREDICTS MICROSATELLITE INSTABILITY IN A POPULATION-BASED SERIES OF COLORECTAL CANCER CASES

2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Population Based ◽  
Pathological Features ◽  
Predictive Tool ◽  
Entire Cohort ◽  
Dna Mismatch ◽  
Bethesda Guidelines ◽  
Revised Bethesda Guidelines

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56

scholarly journals Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer

ESMO Open ◽  
2021 ◽  
Vol 6 (3) ◽  
pp. 100120
Author(s):  
A. Guyot D'Asnières De Salins ◽  
G. Tachon ◽  
R. Cohen ◽  
L. Karayan-Tapon ◽  
A. Junca ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Molecular Testing ◽  
Mismatch Repair Proteins

Does microsatellite instability predict the effect of adjuvant chemotherapy in stage III colorectal cancer? A meta-analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4121-4121
Author(s):  
G. Des Guetz ◽  
B. Uzzan ◽  
P. Nicolas ◽  
K. Chouahnia ◽  
G. Perret ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Colorectal Neoplasm ◽  
Meta Analysis ◽  
Stage Iii ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Electronic Search ◽  
Survival Difference

4121 Background: Microsatellite instability (MSI) is a prognostic factor in colorectal cancer. Whether it predicts the effect of adjuvant chemotherapy (CT) on overall survival (OS) and relapse-free survival (RFS) is controversial. Methods: Studies were identified by an electronic search using online PubMed, with simultaneous keywords (colorectal neoplasm, microsatellite instability, chemotherapy, prognosis). Abstracts from ASCO and AACR proceedings were reviewed. Articles were obtained from cross-checking of references and from a previous prognostic meta-analysis (MA) (Popat, 2005). We used EasyMA software, available online. A Hazard Ratio (HR) < 1 for MSI-high (MSI-H) status compared with microsatellite stable (MSS) meant a better survival. Results: Our MA found 21 studies (4 abstracts). Statistical calculations were performed in 11 studies (5087 patients including 2879 receiving 5FU-based CT; mean age: 63 years; 1489 stage II, 2648 stage III (64%)). MSI-H was found in 644 patients (15% of total), MSS in 3624. Seven studies (2 randomized) assessed 2 cohorts receiving or not adjuvant CT, 4 studies only included patients receiving CT. Global HR OS (9 studies) was 0.79 (95% confidence interval or CI: 0.64–0.98; p = 0.03). Global HR RFS (8 studies) was 0.67 (95% CI: 0.54–0.83; p < 0.001). A MA on stage III patients (4 studies, 719 patients, 137 MSI-H) found a higher survival among MSI-H than MSS patients receiving CT (HR OS: 0.71, 95% CI 0.49–1.03; HR RFS 0.56, 95% CI 0.42–0.75). Interaction between MSI status and CT status was statistically significant on OS and RFS (4 studies). A MA among MSI-H patients (7 studies) found no survival difference between patients under CT or not: HR OS: 0.70 (95% CI 0.44–1.09), HR RFS: 0.96 (95% CI: 0.62–1.49). Conclusions: Adjuvant CT significantly improved survival in MSI-H compared with MSS patients. MSI-H stage III patients receiving CT survived more than MSS. MSI-H status did not predict response to CT compared with no treatment. No significant financial relationships to disclose.

Combined microsatellite instability andBRAFgene status as biomarkers for adjuvant chemotherapy in stage III colorectal cancer

2014 ◽  
Vol 110 (8) ◽  
pp. 982-988 ◽  
Author(s):  
Akira Ooki ◽  
Kiwamu Akagi ◽  
Toshimasa Yatsuoka ◽  
Masako Asayama ◽  
Hiroki Hara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Stage Iii

scholarly journals STAT1 as a potential prognosis marker for poor outcomes of early stage colorectal cancer with microsatellite instability

PLoS ONE ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. e0229252 ◽  
Author(s):  
Atsushi Tanaka ◽  
Yihua Zhou ◽  
Makiko Ogawa ◽  
Jinru Shia ◽  
David S. Klimstra ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Early Stage ◽  
Prognosis Marker ◽  
Poor Outcomes

Microsatellite instability and oral fluoropyrimidine adjuvant chemotherapy in stage II and III colorectal cancer

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 15059-15059
Author(s):  
Y. Kakeji ◽  
E. Oki ◽  
K. Ohgaki ◽  
K. Shibahara ◽  
S. Shiotani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Stage Ii ◽  
Oral Fluoropyrimidine

Molecular Diagnostics of Colorectal Cancer

2011 ◽  
Vol 135 (5) ◽  
pp. 578-587
Author(s):  
Ahmed Bedeir ◽  
Alyssa M. Krasinskas
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Molecular Diagnostics ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Response To Therapy ◽  
Molecular Testing ◽  
Cancer Predisposition Syndrome ◽  
Standard Tool

Abstract Context.—Of all gastrointestinal tract epithelial malignancies, molecular diagnostics has impacted colorectal cancer the most. Molecular testing can detect sporadic and inherited colorectal cancers that arise through the microsatellite instability pathway and can determine the efficacy of targeted drug therapy. Objectives.—To review the microsatellite instability pathway of colorectal carcinoma carcinogenesis and to demonstrate the diagnostic utility of molecular testing in the detection of patients with Lynch syndrome, an inherited disorder of this pathway. Also, to review the significance of detection of KRAS and BRAF gene mutations in predicting the response to anti–epidermal growth factor receptor therapies. Data Sources.—This article is based on original publications and review articles that are accessible through the PubMed biomedical database (US National Library of Medicine). Conclusions.—In modern pathology practice, molecular testing is a standard tool that is used to diagnose an inherited colorectal cancer predisposition syndrome (Lynch syndrome) and to help predict outcome and response to therapy for patients with advanced colorectal cancer.

scholarly journals Adjuvant Chemotherapy in Colorectal Cancer Patients with Microsatellite Instability

2006 ◽  
Vol 12 (12) ◽  
pp. 3866-3867 ◽  
Author(s):  
Toshiaki Watanabe ◽  
Takamitsu Kanazawa ◽  
Yoshihiro Kazama ◽  
Junichiro Tanaka ◽  
Toshiaki Tanaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Colorectal Cancer Patients

Molecular testing guidelines for selection of colorectal cancer patients for targeted and conventional therapies.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 600-600
Author(s):  
Antonia R. Sepulveda ◽  
Stanley R. Hamilton ◽  
Wayne Grody
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Molecular Testing ◽  
Evidence Based ◽  
Biomarker Testing ◽  
Crc Management ◽  
Colorectal Cancer Patients ◽  
Evidence Based Guidelines ◽  
Selection Of

600 Background: Molecular testing to enhance the response of colorectal cancers (CRC) to targeted and conventional therapies has been the center of many recent studies. While testing for KRAS mutations is generally accepted as a requirement to select patients for anti-EGFR antibody therapies, evidence-based guidelines for other markers are needed. The objective of this project is to establish evidence-based recommendations for the molecular testing of CRC tissues to guide EGFR-targeted therapies and conventional chemotherapy regimens. Methods: Three professional societies: American Society of Clinical Pathologists (ASCP), College of American Pathologists (CAP) and the Association for Molecular Pathology (AMP) have selected co-chairs, and multidisciplinary expert and advisory panels, which include specialists in pathology, GI oncology, surgery, gastroenterology and genetics. A systematic review was designed based on five overall key questions: (1) What biomarkers are useful for CRC management (selection of patients for targeted and conventional therapies)? (2) How should tissue specimens be processed for biomarker testing for CRC management?; (3) How should biomarker testing for CRC management be performed? (4) How should molecular testing of CRC be implemented and operationalized?; V: Should other genes/biomarkers be routinely tested? The expert panel will review title-abstract (TA) and full-text (FT) in DistillerSR software. Data extraction will then be performed and the panel will draft recommendations based upon evidence tables and the considered judgment process. Results: A systematic review was performed to capture published articles from January 2009 through August 2013, yielding 2,883titles to date. Currently the TA review phase is in course. Release of draft recommendations during an open comment period is anticipated in early 2014. Conclusions: The ASCP-CAP-AMP Molecular Testing Guidelines for Selection of Colorectal Cancer Patients for Targeted and Conventional Therapies will provide evidence-based guidelines for molecular testing of CRC. The final publication release is anticipated for the fall 2014.

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