Expression of MLH1 and MSH2 in Urothelial Carcinoma of the Renal Pelvis
Laleh Ehsani, Adeboye O Osunkoya. Emory University School of Medicine, Atlanta, GA
Background: Tumors of the renal pelvis account for approximately 7% of all renal tumors, and approximately 5% of all urothelial tumors. Hereditary non polyposis colorectal cancer (HNPCC)/Lynch syndrome is a disorder characterized by mutation or inactivation of a number of DNA mismatch repair genes that encode several proteins of multigene families, including MLH1 and MSH2. In this study we investigated the association between microsatellite instability (MSI) by lack of immunohistochemical staining for MLH1 and MSH2, in urothelial carcinoma (UCA) of the renal pelvis.
Design: The study included 44 cases of UCA of the renal pelvis obtained from radical nephroureterectomy specimens. Clinicopathologic parameters were obtained. All H&E slides were reviewed by a Urologic Pathologist to confirm the presence or absence of an inverted growth pattern. Immunohistochemical staining for MLH1 and MSH2 was performed on all cases. The loss of nuclear immunohistochemical staining of MLH1 and/or MSH2 was indicative of MSI.
Results: Eight of 44 (18%) cases had negative MLH1 expression and 25/44 (57%) cases had negative MSH2 expression. Six of 8 (75%) cases with negative MLH1 expression were male and 2/8 (25%) cases were female. Nineteen of 25 (75%) cases with negative MSH2 expression were male, and 6/25 (24%) cases were female. Seven of 8 (88%) cases with negative MLH1 expression were high grade UCA, and 21/25 (84%) cases with negative MSH2 expression were high grade UCA. Correlation of pathologic stage with negative MLH1 expression was as follows; 1/8 (13%) cases was pTis, 2/8 (24%) cases were pTa, 1/8 (13%) cases was pT1, 1/8 (13%) cases was pT2 and 3/8 (37%) cases were pT3. Correlation of pathologic stage with negative MSH2 expression was as follows; 1/25 (4%) cases was pTis, 7/25 (28%) cases were pTa, 5/25 (20%) cases were pT1, 1/25 (4%) cases was pT2, 10/25 (40%) cases were pT3, 1/25 (4%)cases was pT4. Twenty one of 44 (48%) cases had an inverted growth pattern, of which 3/21 (14%) cases had negative MLH1 expression and 14/21 (67%) cases had negative MSH2 expression.
Conclusions: MSI based on negative expression of MLH1 and MSH2 was more common in male patients with high grade UCA. There is a strong correlation between inverted growth pattern and negative MSH2 expression.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 217, Tuesday Afternoon