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

Abstract

ObjectivesLynch 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.SettingA local population-based study from Northeastern Iran.Participants321 consecutive CRCs and pathology specimen screened between 2013 and 2016.Primary and secondary outcome measuresRetrospectively, 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.ResultsOf 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.ConclusionClinically, 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.

Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC)

“…Using MSI as the initial screening test, a study from Saudi Arabia reported 11.6% MSI cases [27]. In the Iranian population, 10.57% of the early-onset CRCs were dMMRP [28]. A low frequency (8.4%) of dMMRP was reported in a study from Japan [29], which was the first to evaluate the prevalence of dMMRP in CRC in the young Japanese population, suggesting that this low rate might be related to yet-to-be identified genetic or environmental factors.…”

Spatio-temporal Mapping of Breast and Prostate Cancer in South Iran During 2014-2017

“…Hereditary cancer syndromes, a type of inherited disorder in which there is a higher-than-normal risk of certain types of cancer, are caused by mutations in certain genes passed from parents to children (62)(63)(64)(65)(66). Indeed, certain patterns of cancer may be seen within families, e.g., hereditary breast (65) and lynch syndrome (63).…”

Spatio-temporal mapping of breast and prostate cancers in South Iran from 2014-2017

“…Hereditary cancer syndromes, a type of inherited disorder in which there is a higher-than-normal risk of certain types of cancer, are caused by mutations in certain genes passed from parents to children (64)(65)(66)(67)(68).…”