Loss of mismatch-repair protein expression and microsatellite instability in upper tract urothelial carcinoma and clinicopathological implications

Abstract Background Upper tract urothelial carcinoma (UTUC) may arise in the setting of hereditary nonpolyposis colorectal cancer (Lynch syndrome) or sporadically. Variable frequencies of microsatellite instability (MSI) were found in UTUC. For advanced solid MSI tumors targeted therapy with PD-L1 inhibitors is available. Therefore, we aimed to determine the prevalence of mismatch repair (MMR) protein loss and MSI in UTUC using a tissue microarray approach and further molecular and correlation analysis. Materials and Methods We studied the immunohistochemical expression of MLH1, MSH2, MSH6 and PMS2 on tissue microarrays containing formalin-fixed, paraffin-embedded samples of 128 patients with UTUC. MSI analysis was performed in 79 cases with deficient MMR protein expression and/or in patients aged 60 and below and/or other tumors possibly related to Lynch syndrome. Results Loss of MMR protein expression was seen in 24/128 cases (18.8%). MSI analysis revealed MSI-high in 29, MSI-low in 7 cases. Fisher’s test demonstrated significant differences between MSI and loss of MMR protein expression, clinically possible LS, tumor growth pattern, inverted growth pattern, and death (p Conclusion The frequency of MSI in UTUC was 36/128 (28.1%)with a good accuracy of immunohistochemistry. In daily practice, MSI screening especially is recommended in patients with advanced UTUC and inverted papillary tumor growth pattern with the aim of screening patients for possible targeted therapy.