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. 2019 Feb;10(1):19-29.
doi: 10.21037/jgo.2018.10.01.

Low prevalence of deficient mismatch repair (dMMR) protein in locally advanced rectal cancers (LARC) and treatment outcomes

Vikas Ostwal  1 , Nikhil S Pande  1 , Reena Engineer  2 , Avanish Saklani  3 , Ashwin deSouza  3 , Mukta Ramadwar  4 , Suvarna Sawant  4 , Sarika Mandavkar  1 , Sameer Shrirangwar  1 , Pritam Kataria  1 , Prachi Patil  5 , Omshree Shetty  6 , Anant Ramaswamy  1
Affiliations

Low prevalence of deficient mismatch repair (dMMR) protein in locally advanced rectal cancers (LARC) and treatment outcomes

Vikas Ostwal et al. J Gastrointest Oncol. 2019 Feb.

Abstract

Background: The available evidence in locally advanced rectal cancer (LARC) suggests a low prevalence of deficient mismatch repair (dMMR) protein status, approximating 1-3%.

Methods: Patients with LARC who were offered long course chemoradiation (LCRT), as per institution protocol during the period of 1st January 2014 to 31st December 2015 at Tata Memorial Hospital (TMH) in Mumbai were evaluated for outcomes and assessment of MMR status.

Results: A total of 419 patients were evaluated for LARC in TMH, of whom 354 were treated with LCRT. Of these 354 patients, 296 were assessable for MMR status based on tissue adequacy for testing. Three patients (1.01%) has dMMR status, while the remaining 293 patients had proficient MMR status. A total of 240 patients (67.8%) underwent curative intent resections. With a median follow-up of 32 months, estimated 3-year recurrence free survival (RFS) and overall survival (OS) for the resected group was 63.5% and 85.2%, respectively, while 3-year event free survival and OS for the unresected cohort was 15.2% and 15.8%, respectively. Signet ring histology, higher ypT stage, involved margin status post resection, and delays (>1 week) in LCRT were associated with inferior OS on multivariate analysis.

Conclusions: In a large LARC cohort, a majority of tumors had proficient MMR status, suggesting that MSI as a biomarker may have limited applicability in the management of rectal cancers. Signet ring histology, CRM involvement post resection, higher ypT stage and interruptions in LCRT predicted for inferior OS.

Keywords: Mismatch repair (MMR); immunohistochemistry (IHC); neoadjuvant long course chemoradiation (NACTRT); rectal adenocarcinoma; signet ring.

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

References

    1. Boland CR, Goel A. Microsatellite Instability in Colorectal Cancer. Gastroenterology 2010;138:2073-87.e3. 10.1053/j.gastro.2009.12.064 - DOI - PMC - PubMed
    1. Ribic CM, Sargent DJ, Moore MJ, et al. Tumor Microsatellite-Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Colon Cancer. N Engl J Med 2003;349:247-57. 10.1056/NEJMoa022289 - DOI - PMC - PubMed
    1. Sargent DJ, Marsoni S, Monges G, et al. Defective Mismatch Repair As a Predictive Marker for Lack of Efficacy of Fluorouracil-Based Adjuvant Therapy in Colon Cancer. J Clin Oncol 2010;28:3219-26. 10.1200/JCO.2009.27.1825 - DOI - PMC - PubMed
    1. Hutchins G, Southward K, Handley K, et al. Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer. J Clin Oncol 2011;29:1261-70. 10.1200/JCO.2010.30.1366 - DOI - PubMed
    1. The clinical features of rectal cancers with high-frequency microsatellite instability (MSI-H) in Japanese males. Cancer Lett 2004;216:55-62. 10.1016/j.canlet.2004.07.017 - DOI - PubMed