Accuracy of Revised Bethesda Guidelines, Microsatellite Instability, and Immunohistochemistry for the Identification of Patients With Hereditary Nonpolyposis Colorectal Cancer

Abstract

EREDITARY NONPOLYPOSIS COlorectal cancer (HNPCC), also named Lynch syndrome, is an autosomal dominant disorder that accounts for approximately 1% to 3% of all colorectal cancers. 1,2 HNPCC is caused by germline mutations in DNA mismatch repair genes, mainly MSH2 and MLH1. 3 Defects on this pathway lead to changes in the length of nucleotide repeat sequences of tumor DNA, termed microsatellite instability.Although a great advance in the understanding of the molecular basis of HNPCC has taken place in the last decade, optimal selection of individuals for HNPCC genetic testing remains controversial. 4 In 1991, the International See also pp 1979 and 2028.

MSH6 and MUTYH Deficiency Is a Frequent Event in Early-Onset Colorectal Cancer

“…This frequency is consistent with previous reports in which even when patients were selected from high-risk CRC clinics, the mutation detection rate was no more than 50% to 60% (10, 27–30, 34). This fact constitutes a real problem in clinical practice, and in preventive strategies, these cases are usually considered as mutation carriers.…”

The First Molecular Screening of MLH1 and MSH2 Genes in Moroccan Colorectal Cancer Patients Shows a Relatively High Mutational Prevalence

“…The estimated incidence of MLH1/MSH2 germline mutations in our cohort was 1.87%. Our data seem to be quite high compared to the Spanish (0.5% and 0.9%), Japanese (0.4%), and Saudi Arabian (0.7%) populations (Pin ˜ol et al, 2005;Pe ´rez-Carbonell et al, 2012;Siraj et al, 2015;Chika et al, 2016), but were in line with two previous western studies that performed germline LS testing after refinement of patients selection using MSI/IHC tumor testing. Indeed, in a study of 1058 unselected CRC, Yurgelun et al found 20 MLH1/ MSH2 mutation carriers (1.89%), which was similar to our results (Yurgelun et al, 2017).…”

Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer

“…In our 146 patients with colorectal cancers, 34 patients (23.3%) had MSI colorectal cancer. This is comparable to the studies by Pinol et al [ 13 ] and Yearsley et al [ 16 ]. Wong et al [ 17 ] showed that in the case of sporadic endometrial carcinoma, MSI endometrial carcinoma accounted for 26% of patients.…”