Lynch Syndrome (LS), a genetically inherited autosomal disorder, increases the incidence of colorectal carcinoma (CRC). We aimed to perform universal strategy to assess the prevalence and clinicopathological characteristics of early-onset CRCs at high risk of LS vs. late-onset ones in the Iranian population.

Retrospectively, 321 patients with CRC were screened between 2013 and 2016 in Mashhad, Iran. Information regarding the clinical criteria was obtained by interviewing the patients or, their families. Amsterdam II criteria, revised Bethesda guideline, and universal strategy was performed to screen CRCs. Pathologists tested Tumors with IHC staining of four Mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2). Tumors with absent IHC staining of MLH1 were tested for BRAF mutations to exclude sporadic CRCs.

Of 321 CRCs, (13/123 (10.57%) early-onset vs. 21/198 (10.6%) late-onset) were detected to be 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 recognized as sporadic. The difference in outcome of IHC-analysis between early- and late-onset CRCs at high risk of LS was not statistically significant (p-value = 0.34). Majority of the suspected LS tumors 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.

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.