MLH1 and MSH2 mismatch repair protein profile using immunohistochemistry in Nepalese colorectal cancer patients

Abstract

<jats:p>BACKGROUND Hereditary nonpolyposis colorectal cancer, or Lynch syndrome, caused by germline mutations or genetic defects in mismatch repair (MMR) genes (MLH1, MSH2, PMS2, MSH6, and epithelial cellular adhesion molecule), is an autosomal dominant condition accounting for 2–5% of all colorectal carcinomas (CRCs). Reports on MMR loss in many populations are available; however, there are no reports on the frequency of MMR protein expression in Nepalese cohorts. Therefore, this study was aimed to assess the expression profiles of MLH1 and MSH2 protein by immunohistochemistry (IHC) in Nepalese CRC patients.&#x0D; METHODS This retrospective study used archived formalin-fixed paraffin-embedded tissue blocks from 43 Nepalese CRC patients. IHC staining was performed using MLH1 and MSH2 antibodies. IHC scoring analysis was assessed using semiquantitative scoring.&#x0D; RESULTS Of the 43 CRC patients, 8 (18.6%) showed loss of staining for MLH1 antibody, 5 (11.6%) showed loss of staining for MSH2 antibody, and 4 (9.3%) showed loss of staining for both MLH1 and MSH2 antibodies.&#x0D; CONCLUSIONS IHC is a potential screening method of determining the MMR expression profile of Nepalese CRC patients. IHC can be performed in local clinical laboratories to find MMR protein defects in selected cases prior to expensive molecular tests.</jats:p>

Identification of SNPs in hMSH3/MSH6 interaction domain affecting the structure and function of MSH2 protein

“…Several polymorphism studies have shown the strong association of SNPs toward the susceptibility of cancer. 9,10 Elek et al 11 have recently demonstrated that SNP rs34944508 influences MGAT5 expression, which catalyzes the addition of Nacetylglucosamine (GlcNAc) in β [1][2][3][4][5][6] linkage to mannose of N-linked oligosaccharide, which is a characteristic of invasive lung malignancies. A study conducted by Slovakova et al 12 on promoter polymorphisms for selected MMR genes viz MSH2 (rs2303425) has evaluated the risk of cancer development in both dominant and recessive genetic models and demonstrated that polymorphism of MMR genes MSH2 is associated with a risk of developing sporadic cancer and hereditary tumors in Slovak people.…”

“…MutS Homolog 2 (MSH2) protein plays an essential role in DNA repair and is associated with different cancer such as hereditary nonpolyposis colorectal cancer (HNPCC), Lynch syndrome, and lung cancer 1–3 . MSH2 comprises two interaction domains (MSH3/MSH6 and MSH2/PMS2) and one DNA binding domain, which are present in two different locations on the gene (Figure 1).…”

“…Elek et al 11 . have recently demonstrated that SNP rs34944508 influences MGAT5 expression, which catalyzes the addition of N‐acetylglucosamine (GlcNAc) in β 1–6 linkage to mannose of N‐linked oligosaccharide, which is a characteristic of invasive lung malignancies. A study conducted by Slovakova et al 12 .…”