Expression of Mismatch Repair Proteins in Early and Advanced Gastric Cancer in Poland

Abstract

BackgroundMutations in DNA of mismatch repair (MMR) genes result in failure to repair errors that occur during DNA replication in microsatellites, resulting in accumulation of frameshift mutations in these genes and leading to DNA mismatch replication errors and microsatellite instability. Gastric cancers (GCs) with high MSI (MSI-H) are a well-defined subset of carcinomas showing distinctive clinicopathological features. In this study we investigated the rate of MSI and the correlation between MSI status and clinicopathological features of GC.Material/MethodsThe study included 107 patients with GCs: 61 with advanced gastric cancers (AGC) and 46 with early gastric cancer (EGC). MSI deficiency in GCs was assessed by the immunohistochemical analysis of expression of MMR proteins – MLH1, MSH2, MSH6, and PMS2 – using formalin-fixed and paraffin-embedded tissue.ResultsA total of 6 (5.6%) MSI-H were observed. The loss of MMR proteins expression was associated with the intestinal type of GC in Lauren classification, and tubular and papillary architecture in WHO classification. There was no statistically significant association between negative MMR expression and other selected clinical parameters: age, sex, tumor location, depth of invasion (EGC and AGC), lymph nodes status, presence of the ulceration, and lymphocytic infiltrate.ConclusionsIn the present era of personalized medicine, the histological type of GC and MMR proteins status in cancer cells are very important for the proper surveillance of patients with familial GC and sporadic GCs, as well as for selecting the proper follow-up and treatment. Larger collaborative studies are needed to verify the features of MSI-H GCs in Poland.

Implication of expression of MMR proteins and clinicopathological characteristics in gastric cancer

“…The work presented here explored the prevalence of loss of MMR proteins in gastric cancer. The percentage (40%) of patients who revealed the loss of one or more MMR proteins is relatively high as compared to other studies demonstrating varying degree (5.6%-30%) of defective MMR expression all over the world in GC [15,16,18,22]. This observation suggests demographic and genetic factors prevailing in human populations contribute towards these variations.…”

“…Loss of MMR protein expression has been recorded in up to 30% of GC cases [14][15][16][17][18]. In the present study, we have reported the expression of four mismatch repair proteins, MLH1, MSH2, MSH6, and PMS2 in GC using an immunohistochemical staining procedure in Indian population along with the association of clinical parameters of GC patients with loss of expression of mismatch repair proteins.…”

“…The expression of proteins implicated in mismatch repair mechanism has always been an area of interest for cancer researchers. MSI in MMR proteins has been unveiled in various studies from different regions of the world, shedding light on the expressional analysis of MMR proteins including four major proteins-MLH1, MSH2, MSH6, and PMS2 [17][18][19][20]. Microsatellite instability panel of five markers given by Bethesda has been found associated with expression MMR protein (MLH1 and PMS2) in 88% cases, indicating a strong correlation between MMR protein expression and underlying genetic mutation at microsatellite loci [19].…”

Microsatellite Instability and Altered Expressions of MLH1 and MSH2 in Gastric Cancer

“…But, MSI positive tumours were more frequently located at the distal of the stomach and most of them were intestinal type by Laurén classifications and these observations are in line with previous study displayed MSI-H groups that represented loss of MMR proteins and associated with intestinal type. This also indicated its association with overall good prognosis (Karpinska-Kaczmarczyk et al, 2016). However, these data warrant a larger number of GCs samples for further evaluation to elucidate distinct prognosis between MSI tumours and clinicopathological characteristics.…”

“…In this study, however determining affected MMR genes by IHC using MLH1 and MSH2 antibodies may lead to false negative MSI. It has been shown that PCR-based MSI detection was relatively low in GC, however higher prevalence of MLH1 and PMS2 were observed (Karpinska-Kaczmarczyk et al, 2016;Mathiak et al, 2017). Therefore, four antibodies panel (MLH1, MSH2, PMS2 and MSH6) are compulsory panel markers for further evaluation in order to increase sensitivity of IHC as predictive value that is almost equivalent to that of MSI analysis.…”