Mismatch Repair Status and Associated Clinicopathological Factors Among Young-Onset Colorectal Carcinoma
DOI:
https://doi.org/10.21276/apalm.3424Keywords:
Mismatch repair genes, microsatellite instability, IHC, young-onset CRCAbstract
Background: Microsatellite instability (MSI) forms an important pathway in the pathogenesis of colorectal carcinoma (CRC). CRC with MSI is termed MMR-deficient (dMMR), and those with intact MMR genes are termed MMR-proficient (pMMR). The objective of the study is to determine the proportion of pMMR and dMMR among young-onset CRC patients and to evaluate the association of the clinicopathological profile with MMR status.
Materials and Methods: This retrospective cross-sectional study was carried out in the Department of Pathology, RIMS Imphal, among patients diagnosed with CRC below 45 years of age from March 2021 to February 2023. The slides were re-evaluated regarding tumor types, grade, presence of lymphovascular invasion (LVI), and tumor-infiltrating lymphocytes (TILs). IHC staining was performed using antibodies MLH1, PMS2, MSH2, and MSH6. Loss of nuclear expression in all or any one of the antibodies was termed dMMR, whereas intact nuclear expression of all four antibodies was labeled pMMR.
Results: A total of 44 cases were included in the study, of which 36 (81.82%) were pMMR and 8 (18.18%) were dMMR. The dMMR group had a mean age of 37.1 years, with a male preponderance (62.50%). The ascending colon was the most common site (50.00%), 62.50% presented as advanced disease (stage IV), 50.00% were moderately differentiated, 37.50% had mucinous morphology, and 62.50% showed the presence of TILs.
Conclusion: A significant proportion of young-onset CRC in our study population demonstrated dMMR status. dMMR CRC had a higher histological grade, mostly presenting at an advanced stage.
References
1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87–108.
2. Sacdalan DL, Garcia RL, Diwa MH, Sacdalan DB. Clinicopathologic factors associated with mismatch repair status among Filipino patients with young-onset colorectal cancer. Cancer Manag Res. 2021 Mar 1;13:2105–15.
3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7–30.
4. Hashmi AA, Bukhari U, Rizwan R, Faisal F, Kumar R, Malik UA, et al. Mismatch repair deficient (dMMR) colorectal carcinoma in a Pakistani cohort: association with clinical and pathological parameters. Cureus. 2023 Aug 1;15(8):e42781.
5. Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010 Jun;138(6):2073–87.e3.
6. Hashmi AA, Ali R, Hussain ZF, Faridi N, Khan EY, Bakar SMA, et al. Mismatch repair deficiency screening in colorectal carcinoma by a four-antibody immunohistochemical panel in Pakistani population and its correlation with histopathological parameters. World J Surg Oncol. 2017 Jun 26;15(1):116.
7. De' Angelis GL, Bottarelli L, Azzoni C, De' Angelis N, Leandro G, Di Mario F, et al. Microsatellite instability in colorectal cancer. Acta Biomed. 2018 Dec;89(9-S):97–101.
8. Vilar E, Gruber SB. Microsatellite instability in colorectal cancer—the stable evidence. Nat Rev Clin Oncol. 2010 Mar;7(3):153–62.
9. Mei WJ, Mi M, Qian J, Xiao N, Yuan Y, Ding PR. Clinicopathological characteristics of high microsatellite instability/mismatch repair-deficient colorectal cancer: a narrative review. Front Immunol. 2022 Dec 23;13:1019582.
10. Lee CT, Chow NH, Chen YL, Ho CL, Yeh YM, Lin SC, et al. Clinicopathological features of mismatch repair protein expression patterns in colorectal cancer. Pathol Res Pract. 2021 Jan;217:153288.
11. Marra G, Boland CR. Hereditary nonpolyposis colorectal cancer: the syndrome, the genes, and historical perspectives. J Natl Cancer Inst. 1995 Aug 2;87(15):1114–25.
12. Kawakami H, Zaanan A, Sinicrope FA. Microsatellite instability testing and its role in the management of colorectal cancer. Curr Treat Options Oncol. 2015 Jul;16(7):30.
13. Wolf AMD, Fontham ETH, Church TR, Flowers CR, Guerra CE, LaMonte SJ, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018 Jul;68(4):250–81.
14. Kaur G, Masoud A, Raihan N, Radzi M, Khamizar W, Kam LS. Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma. Indian J Med Res. 2011 Aug;134(2):186–92.
15. Rios-Valencia J, Cruz-Reyes C, Galindo-García TA, Rosas-Camargo V, Gamboa-Domínguez A. Mismatch repair system in colorectal cancer. Frequency, cancer phenotype, and follow-up. Rev Gastroenterol Mex (Engl Ed). 2022 Oct-Dec;87(4):432–8.
16. Park SK, Park DI, Park SH, Park JH, Kim HJ, Cho YK, et al. Microsatellite instability in young patients with sporadic colorectal adenomas. Hepatogastroenterology. 2011 Sep-Oct;58(110–111):1531–7.
17. Li C, Liu F, Huang D, Wu Y, Wang Z, Xu Y. The correlation between DNA mismatch repair status and the clinicopathological and molecular features of Chinese sporadic colorectal cancer. Transl Cancer Res. 2020 Jan;9(1):137–44.
18. Ye JX, Liu Y, Qin Y, Zhong HH, Yi WN, Shi XY. KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients. World J Gastroenterol. 2015 Feb;21(5):1595–605.
19. Takemoto N, Konishi F, Yamashita K, Kojima M, Furukawa T, Miyakura Y, et al. The correlation of microsatellite instability and tumor-infiltrating lymphocytes in hereditary non-polyposis colorectal cancer (HNPCC) and sporadic colorectal cancers: the significance of different types of lymphocyte infiltration. Jpn J Clin Oncol. 2004 Feb;34(2):90–8.
20. Smyrk TC, Watson P, Kaul K, Lynch HT. Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma. Cancer. 2001 Jun;91(12):2417–22.
21. Ryan E, Sheahan K, Creavin B, Mohan HM, Winter DC. The current value of determining the mismatch repair status of colorectal cancer: a rationale for routine testing. Crit Rev Oncol Hematol. 2017 Aug;116:38–57.
22. Guastadisegni C, Colafranceschi M, Ottini L, Dogliotti E. Microsatellite instability as a marker of prognosis and response to therapy: a meta-analysis of colorectal cancer survival data. Eur J Cancer. 2010 Oct;46(15):2788–98.
23. Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005 Jan 20;23(3):609–18.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Rajesh Singh Laishram, Thingujam Deeparani, Laishram Deepak Kumar, Thokchom Sylvia, Mautoshi Debnath, Sushma Khuraijam
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access at http://opcit.eprints.org/oacitation-biblio.html).
