Prevalence and clinicopathological characteristics of mismatch repair-deficient colorectal carcinoma in early onset cases as compared with late-onset cases: A retrospective cross-sectional study in Northeastern Iran

Goshayeshi, L. and Ghaffarzadegan, K. and Khooei, A. and Esmaeilzadeh, A. and Rahmani Khorram, M. and Mosannen Mozaffari, H. and Kiani, B. and Hoseini, B. (2018) Prevalence and clinicopathological characteristics of mismatch repair-deficient colorectal carcinoma in early onset cases as compared with late-onset cases: A retrospective cross-sectional study in Northeastern Iran. BMJ Open, 8 (8).

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Prevalence and clinicopathological characteristics of mismatch repair-deficient colorectal carcinoma in early onset cases as compared with late-onset cases A retrospective cross-sectional study in Northeastern Iran.pdf

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Abstract

Objectives Lynch syndrome (LS), a genetically inherited autosomal disorder, increases the incidence of colorectal carcinoma (CRC). We aimed to perform a universal strategy to assess the prevalence and clinicopathological characteristics of early onset CRCs at high risk of LS versus late-onset ones in the Iranian population. Setting A local population-based study from Northeastern Iran. Participants 321 consecutive CRCs and pathology specimen screened between 2013 and 2016. Primary and secondary outcome measures Retrospectively, information regarding the clinical criteria was obtained by interviewing the patients with CRC or, their families. Pathologists tested tumours with immunohistochemistry (IHC) staining of four mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2). Tumours with absent IHC staining of MLH1 were tested for BRAF mutations to exclude sporadic CRCs. Prevalence of early onset CRCs at high risk of LS and familial CRC type X were assessed as primary and secondary outcome measures, respectively. Results Of 321 CRCs (13/123 (10.57), early onset vs 21/198 (10.6) late-onset) were detected to be MMR-deficient (dMMR). Nine early onset cases and 14 late-onset ones with a loss of MLH1 underwent testing for the BRAF mutation, none of the early onset and four (2.02) late-onset were recognised as sporadic. The difference in the outcome of IHC-analysis between early and late-onset CRCs at high risk of LS was not statistically significant (p=0.34). Majority of the suspected LS tumours from early onset patients had arisen in distal part (8/11 (72.72) vs 8/14 (57.14)), all of which were occurred in the rectum or sigmoid. Conclusion Clinically, these findings suggest that in case of limitation for BRAF testing, the practitioner in Iran may consider managing early onset dMMR cases like LS until access to BRAF testing becomes available to them, before germline testing to accurately diagnose LS. © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Item Type: Article
Additional Information: Cited By :2 Export Date: 16 February 2020 Correspondence Address: Hoseini, B.; Department of Health Information Technology, Neyshabur University of Medical SciencesIran; email: binyamin.hoseini@gmail.com
Uncontrolled Keywords: colorectal cancer early onset immunohistochemistry lynch syndrome mismatch repair B Raf kinase DNA mismatch repair protein MSH2 mismatch repair protein PMS2 MutL protein homolog 1 protein MSH6 adult aged Article colorectal carcinoma controlled study cross-sectional study early onset carcinoma family history female gene mutation hereditary nonpolyposis colorectal cancer high risk patient human Iran late onset disorder major clinical study male onset age population research prevalence retrospective study colorectal tumor comparative study complication genetics middle aged pathology risk factor Age of Onset Colorectal Neoplasms Colorectal Neoplasms, Hereditary Nonpolyposis Cross-Sectional Studies DNA Mismatch Repair Humans Retrospective Studies Risk Factors
Subjects: WI Digestive System
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 20 May 2020 05:29
Last Modified: 20 May 2020 05:29
URI: http://eprints.mums.ac.ir/id/eprint/17304

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