Mehta A, Bansal D, Tripathi R, Anoop V. Phenotypic attributes and survival in mismatch repair deficient/microsatellite instability-high colorectal carcinomas. World J Clin Oncol 2025; 16(6): 104243 [DOI: 10.5306/wjco.v16.i6.104243]
Corresponding Author of This Article
Divya Bansal, MD, Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini Sector 5, New Delhi 110085, Delhi, India. divyabansalrgci@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Anurag Mehta, Department of Laboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi 110085, Delhi, India
Divya Bansal, Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi 110085, Delhi, India
Rupal Tripathi, Vidya Anoop, Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi 110085, Delhi, India
Author contributions: Mehta A conceptualized the study; Bansal D, Tripathi R, and Anoop V performed the data curation; Mehta A and Bansal D performed the formal analysis and reviewed and edited the manuscript; Bansal D and Tripathi R prepared the original draft; and all authors thoroughly reviewed and endorsed the final manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Rajiv Gandhi Cancer Institute and Research Centre, approval No. Res/SCM/49/2021/160.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data is available with all the authors and can be provided on request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Divya Bansal, MD, Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini Sector 5, New Delhi 110085, Delhi, India. divyabansalrgci@gmail.com
Received: December 16, 2024 Revised: March 20, 2025 Accepted: May 7, 2025 Published online: June 24, 2025 Processing time: 188 Days and 3.5 Hours
Abstract
BACKGROUND
Mismatch repair deficient/microsatellite instability-high (MMR-D/MSI-H) colorectal cancers (CRCs) possess a distinctive genomic profile that results in a spectrum of phenotypic attributes setting them apart from their mismatch repair proficient (MMR-P) or microsatellite stable (MSS) counterparts. CRCs have several prognostic factors, including stage, tumor differentiation, location, lymphovascular and perineural invasion, tumor budding, tumor infiltrating lymphocytes, lymph node yield (LNY), and lymph node ratio (LNR).
AIM
To determine the unique phenotypic characteristics of MMR-D/MSI-H CRCs and leverage the conventional wisdom of LNY and LNR with the distinctive characteristics of MMR-D/MSI-H CRCs.
METHODS
This retrospective analysis involved 223 stage I-III CRC patients who underwent surgical resection without neoadjuvant treatment. Clinical and histological features were obtained from patient records and by re-examining the hematoxylin and eosin-stained slides. MMR/MSI status was evaluated for all patients using either MMR immunohistochemistry or MSI testing.
RESULTS
Of the 223 patients in our study, 87 (39.01%) were MMR-D/MSI-H CRCs while 136 (60.99%) were MMR-P/MSS CRCs. The MMR-D/MSI-H CRCs exhibited significant statistical differences compared to the MMR-P/MSS CRCs in several factors, including location, stage, tumor budding, lymphovascular and perineural invasion, lymphocytic response, LNY, LNR, and size of uninvolved lymph nodes. LNY and LNR were significantly higher in MMR-D/MSI-H group compared with the MMR-P/MSS group (P = 0.003 and P < 0.001, respectively). Also, the interquartile range of the largest uninvolved lymph node was 1 cm (0.8 cm-1.2 cm) in MMR-D/MSI-H CRCs compared to 0.7 cm (0.6 cm-0.97 cm) in MMR-P/MSS CRCs. The overall survival for the MMR-P/MSS CRC group was 71% at five years, and the MMR-D/MSI-H CRC group was 92% at five years (P < 0.001).
CONCLUSION
MMR-D/MSI-H CRCs possess a unique genomic profile that leads to distinct phenotypic characteristics, including an enhanced immune response. This distinctive profile underscores the substantial prognostic and predictive value of MMR-D/MSI-H status in CRC.
Core Tip: Mismatch repair deficient/microsatellite instability-high (MMR-D/MSI-H) colorectal cancers (CRCs) account for 15% of CRCs exhibiting peculiar clinicopathological features. The correlation between MMR-D/MSI-H status and distinct lymph node characteristics, including increased lymph node yield, low lymph node ratio, and larger uninvolved node size, suggests a potential link to the heightened immune response typical of these cancers. These findings reinforce the promising prognosis associated with MMR-D/MSI-H CRC, reflecting improved overall survival rates compared to mismatch repair proficient or microsatellite stable tumors and offering valuable insights for tailored therapeutic approaches in this specific subtype of CRC.
