Untersuchung der MDR1-Expression und ihrer klinischen Relevanz beim Keimzelltumor des Hodens

The multidrug resistance protein 1 (MDR1, P-gp, p-170) is a membrane glycoprotein that acts as an energy-dependent drug efflux pump. In various malignancies its expression is associated with resistance to diverse cytostatic drugs, and therefore predicts resistance to systemic treatment. The aim of this study was to investigate the prognostic value of MDR1 expression in primary tumour tissue to predict necrosis or viable cancer in residual tumour masses after systemic chemotherapy for advanced tescticular germ cell cancer. Out of 77 patients, histopathological characteristics of primary testicular cancer specimens and retroperitoneal lymph node dissection (RPLND) samples following chemotherapy were available from 72 and all 77 patients, respectively, 17 (23,6%) with seminoma and 55 (76,4%) with non-seminoma. Out of the 55 patients with non-seminoma 30 (16,5%) showed mature teratoma in the primary tumour of the testis. Moreover, MDR1expression was determined by immunohistochemistry in 47 primary tumours and corresponding 73 RPLND sections. Regarding the pimary tumour we found no MDR1-expression in 24 (51,1%) patients, weak/intermediate expression of MDR1 was found in 5 (10,6%) and strong MDR1-expresson in 18 (38,3%) patients, respectively. Out of the 73 RPLND sections 18 (24,7%) showed a weak/intermediate MDR1-expression and 8 (11%) a strong MDR1-expresion, respectively. Sections containing necrosis showed no MDR1-expression at all. After chemotherapy and subsequent RPLND, the examination of residual tumour masses revealed that mature teratoma and active viable tumour were predominantly found in patients with non-seminoma (NSGCT; p=0.048), especially in those with containing mature teratoma (p=0.001). Moreover, using univariate analysis the expression of MDR1 in the primary testicular tumour predicted viable tumour / teratoma residues in RPLND sections (p=0.003). However, in multivariate analysis including the tumours’ histological subtype, MDR1 expression alone failed to reach statistical significance as an independent prognostic marker for residual vital tumour (p≥0.16). With the limited number of patients given, the correlation between MDR1 expression in primary testis cancer and active residual retroperitoneal disease after chemotherapy failed to reach statistical significance as in independent marker. Therefore, up to now routine MDR1 staining of testicular germ cell cancer samples should not be performed in clinical practice. However, as there was a clear trend, a larger number of patients suffering from metastatic non-seminomas shoud be studied, as MDR1 expression might have significant prognostic value in this particular subgroup of patients.