Evaluation of microsatellite instability and tissue expression levels of MLH1, PMS2, MSH2, MSH6 proteins in wilms tumor

Objective: The importance of microsatellite instability (MSI) and mismatch repair genes (MMR) has not been fully elucidated in Wilms tumor (WT) although it was well defined in colorectal cancer in concept of Lynch syndrome. The aim of this study was to determine the prognostic value of MSI and MMR proteins in WT.Method: This study included 45 nephroblastoma cases of childhood. The expressions of MMR proteins were determined using an immunohistochemical method on archival tissue sections. Real Time PCR melting analysis and fluorescence capillary electrophoresis (FCE) were performed for MSI representing BAT25, BAT26, NR21, NR24, mono27, penta D and PentaC genes on the extracted DNA comparing tumor and normal tissues for each case. All results were evaluated statistically.Results: Low MSI was observed in 6 cases (13.3%). There were no statistical correlations between with MSI and some clinical prognosis factors such as stage and survive. Nineteen tumors (42.2%) showed loss of protein expressions of MLH1, PMS2, MSH2 or MSH6. MMR protein defects were correlated with size of tumor (p=0.020), stage (0.019) and survival (p<0.01). Similarly MSI was correlated with the size of the tumor (p=0.046). But there was no relationship between MSI and MMR protein defects (p= 0.198).Conclusion: This study showed that a small proportion of WT might be associated with MSI as defects of DNA mismatch repair genes in pathogenesis. But there was no concordance with the tissue expression of MMR proteins and MSI. These findings suggest that the MMR genes may play an important role in WT evolution with different pathway.