DNA Mismatch Repair Deficiency in Urothelial Carcinoma: An Immunohistochemical Study in Upper Versus Lower Genitourinary Tract Tumors
Lan L Gellert, Rohit Mehra, Jinru Shia, Ying-Bei Chen, Anuradha Gopalan, Samson Fine, Satish Tickoo, Victor E Reuter, Hikmat Al-Ahmadie. MSKCC, New York, NY
Background: The loss of mismatch repair proteins (MMR) has been reported in Lynch syndrome (LS)-associated as well as sporadic urothelial carcinoma (UC). Few studies have focused on the expression of MMR proteins in UC with different histological grade and/or location.
Design: We retrospectively identified 88 UC cases, including 41 bladder tumors and 47 upper tract (ureter and renal pelvis) tumors. MMR proteins (MLH1, MSH2, MSH6, and PMS2) were evaluated by immunohistochemistry (IHC) on whole sections. Abnormal staining was defined as total loss of protein in the tumor with appropriate internal control. The IHC findings were correlated with clinical and pathological characteristics.
Results: In upper tract tumors, loss of MMR proteins was detected in 4 of 47 cases (8.5%). Two of these 4 cases lost both MSH2 and MSH6 proteins. The other 2 cases lost MSH2 and less than 1% of the tumors cells showed weak nuclear staining for MSH6.
In bladder urothelial carcinoma, loss of MMR proteins were detected in 2 of 41 cases (5%); one tumor lost both MSH2 and MSH6 proteins, and the other tumor lost both PMS2 and MLH1 proteins.
The loss of MMR protein expression was present in both non-invasive and invasive components. In the normal urothelium adjacent to the tumor, all MMR proteins were retained. Tumors of both low grade and high grade morphology showed loss of MMR protein expression. Detailed results are summarized in table 1.
|Tumor||Grade||N||Loss of MSH2/MSH6||Loss of MLH1/PMS2|
|Renal pelvis UC||High grade||33||1||0|
|Ureter UC||High grade||8||1||0|
|Bladder UC||High grade||39||1||1|