Dataset Information

Prognostic and Predictive Values of Mismatch Repair Deficiency in Non-Metastatic Colorectal Cancer.

ABSTRACT: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Universal MMR/MSI testing is standard of care for all patients with newly diagnosed CRC based on multi-society guidelines in the United States. Such testing is intended to identify patients with Lynch Syndrome due to a germline mutation in an MMR gene, but also detects those with sporadic dMMR/MSI-high CRCs. The prognostic utility of MMR/MSI status in non-metastatic colorectal cancer has been studied extensively, yet more limited data are available for its predictive utility. Results have not been entirely consistent due to potential stage-related differences and limited numbers of dMMR/MSI-H patients included in the studies. In this review, we summarize the current evidence for the prognostic and predictive value of dMMR/MSI-H in non-metastatic CRC, and discuss the use of this biomarker for patient management and treatment decisions in clinical practice.

SUBMITTER: Jin Z

PROVIDER: S-EPMC7830023 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Prognostic and Predictive Values of Mismatch Repair Deficiency in Non-Metastatic Colorectal Cancer.

Jin Zhaohui Z Sinicrope Frank A FA

Cancers 20210115 2

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Universal MMR/MSI testing is standard of care for all patients with newly diagnosed CRC based on multi-society guidelines in the United States. Such testing is intended to identify patients with Lynch Syndrome due to a germline mutation in an MMR gene, but also detects those with sporadic dMMR/MSI-high CRCs. The prognostic utility of MMR/MSI status in non-metastatic colorectal cancer has been studied extensively, yet ...[more]

PMID: 33467526

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Project description:BackgroundMismatch-repair deficiency (dMMR) predicts worse chemoresponsiveness but better survival in early-stage colorectal adenocarcinoma. This study examined metastatic colorectal and appendix cancers with and without peritoneal metastasis (PM) in the National Cancer Database (NCDB), hypothesizing that dMMR tumors show better survival.MethodsStage 4 colon, rectum, and appendix cancers (2010-2016) were identified in the NCDB (including goblet cell carcinoids, excluding neuroendocrine tumors). Stage 4 disease without liver, bone, brain, lung, or distant nodal metastases defined PM. Fisher's exact tests were used to compare proportions, and Kaplan-Meier analysis was used to evaluate survival.ResultsOf 130,125 stage 4 colon, rectum, and appendix cancers, 27,848 (21.4%) had PM. Appendix primary tumors had PM more commonly than colon or rectum cancer (83.6% vs. 20.6% and 12.1% of stage 4 cases; p < 0.0001). More PM patients had MMR testing than patients with other metastasis (OM) (21.4% vs. 16.1%), and testing increased from 9.6% in 2010 to 26.3% in 2016 (both p < 0.0001). Among the PM patients, MMR testing was least common for appendix cancers (9.0%). When tested, PM patients more often had dMMR (22.9% [1122/4900] vs. 15.4% [2532/16,495] of OM patients; p < 0.0001). Colon primary tumor had dMMR most frequently (25.0% vs. 14.6% and 14.5% for rectal and appendix tumor; p < 0.0001). Most PM patients received chemotherapy (66.2%). Immunotherapy use increased over time (1.1% of PM diagnoses in 2010 vs. 20.8% in 2016). For MMR-tested stage 4 patients, dMMR correlated with worse survival (median OM, 19.7 vs. 23.9 months, p < 0.0001; median PM, 19.9 vs. 24.6 months, p = 0.035).ConclusionsThe NCDB showed dMMR predicting worse survival for stage 4 colorectal cancers with and without PM and dMMR existing in 14.5-25% of tested patients, suggesting that increased attention to MMR testing in stage 4 colorectal and appendix cancers can identify many patients who could potentially benefit from immunotherapy.

Project description:BackgroundThe landscape of hereditary syndromes and clinicopathologic characteristics among US Latino/Hispanic individuals with colorectal cancer (CRC) remains poorly understood.MethodsA total of 265 patients with CRC who were enrolled in the Hispanic Colorectal Cancer Study were included in the current study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data were abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods.ResultsThe mean age of the patients at the time of diagnosis was 53.7 years (standard deviation, 10.3 years), and 48.3% were female. Overall, 21.2% of patients reported a first-degree or second-degree relative with CRC; 3.4% met Amsterdam I/II criteria. With respect to Bethesda guidelines, 38.5% of patients met at least 1 criterion. Of the 161 individuals who had immunohistochemistry and/or microsatellite instability testing performed, 21 (13.0%) had mismatch repair (MMR)-deficient (dMMR) tumors. dMMR tumors were associated with female sex (61.9%), earlier age at the time of diagnosis (50.4 ± 12.4 years), proximal location (61.9%), and first-degree (23.8%) or second-degree (9.5%) family history of CRC. Among individuals with dMMR tumors, 13 (61.9%) had a germline MMR mutation (MutL homolog 1 [MLH1] in 6 patients; MutS homolog 2 [MSH2] in 4 patients; MutS homolog 6 [MHS6] in 2 patients; and PMS1 homolog 2, mismatch repair system component [PMS2] in 1 patient). The authors identified 2 additional MLH1 mutation carriers by genetic testing who had not received immunohistochemistry/microsatellite instability testing. In total, 5.7% of the entire cohort were confirmed to have Lynch syndrome. In addition, 6 individuals (2.3%) had a polyposis phenotype.ConclusionsThe percentage of dMMR tumors noted among Latino individuals (13%) is similar to estimates in non-Hispanic white individuals. In the current study, the majority of individuals with dMMR tumors were confirmed to have Lynch syndrome. Cancer 2017. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Cancer 2017;123:3732-3743. © 2017 American Cancer Society.

Dataset Information

Prognostic and Predictive Values of Mismatch Repair Deficiency in Non-Metastatic Colorectal Cancer.

Publications

Prognostic and Predictive Values of Mismatch Repair Deficiency in Non-Metastatic Colorectal Cancer.

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