Katarzyna Karpińska-Kaczmarczyk, Magdalena Lewandowska, Małgorzata Ławniczak, Andrzej Białek, Elżbieta Urasińska
(Department of Pathology, Pomeranian Medical University, Szczecin, Poland)
Med Sci Monit 2016; 22:2886-2892
Mutations 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 AND METHODS: The 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.
RESULTS: A 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.
CONCLUSIONS: In 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.
Keywords: DNA-Binding Proteins - metabolism, DNA Mismatch Repair, Aged, Female, Gene Expression Regulation, Neoplastic, Humans, Male, microsatellite instability, Middle Aged, Mismatch Repair Endonuclease PMS2 - metabolism, MutL Protein Homolog 1 - metabolism, MutS Homolog 2 Protein - metabolism, Poland, Stomach Neoplasms - metabolism, Transcriptome - genetics