Mismatch Repair Gene Expression In Testicular Germ Cell Tumors And Retroperitoneal Lymph Node Metastasis

Abstract

Abstract Introduction/Objective Testicular germ cell tumors (TCGT) with somatic mismatch repair pathway defects have shown to have worse prognosis and response to therapy. Immunohistochemical staining pattern of MMR panel was classified in a previous study as low (absent or minimal) and high staining (moderate or high staining), with the low staining pattern suggestive of poor prognosis and high risk of recurrence. Herein, we studied the MMR staining pattern in TGCT and lymph node metastasis. Methods 21 TGCT were included in the study: 10 primary testicular tumors and 11 unrelated retroperitoneal lymph node metastasis. All cases were analyzed for MMR protein expression by immunohistochemistry. Clinical, histopathological and follow-up was obtained in all cases. Retained MLH1, MSH2, MSH6, and PMS2 was defined as nuclear staining. Loss of expression was defined as absence of nuclear staining within tumor cells with retained expression in internal control cells, including benign testicular tissue, stromal cells, and infiltrating lymphocytes. Results All primary testicular tumors were mixed GCT: embryonal carcinomas was present in 5, yolk sac tumor in 3 and teratoma in 6 cases. One (10%) of the primary tumors showed focal loss of MLH1 and PMS2 expression in a focus of embryonal carcinoma. All lymph node metastases consisted of teratoma. Seven (64%) metastatic cases showed scattered areas of focal MLH1 loss, 5 (45%) of which showed also focal loss of PMS2. High staining for MSH2 and MSH6 was detected in all 21 cases. Conclusion In our small cohort, focal loss of MLH1 and PMS2 was detected in 10% of primary TGCT, compared to focal loss of MLH1 and PMS2 is 64% and 45%, respectively, of metastatic tumors, suggesting a possible relationship between heterogeneous MLH1 and PMS2 expression and retroperitoneal lymph node metastasis. The current cohort will be expanded to include additional cases.