IS THE EXPRESSION OF MULTIDRUG-RESISTANCE GENE-PRODUCT A PROGNOSTIC INDICATOR FOR THE CLINICAL OUTCOME OF PATIENTS WITH RENAL-CANCER

Objective To determine the significance of the expression of the multi drug resistance gene product (MDR-1) for the aggressiveness of renal c ell carcinoma (RCC). Patients and methods The study comprised 31 patie nts with clinically locally confined RCC treated with radical. nephrec tomy (mean age 64.1 years, range 41-78; mean follow-up 5.4 years, rang e 4.3-7.3). Their survival time and disease-free period were evaluated retrospectively. The expression of the MDR-1 gene product was determi ned immunohistochemic ally using the JSB-1 antibody in formalin-fixed paraffin-embedded tumour samples from these patients. The significance of this variable and tumour stage and malignancy grade was assessed f or predicting the survival and disease-free period using Kaplan-Meier plots (log-rank test or Tarone's test) and the Cox multiple hazard reg ression analysis. Results In a univariate analysis, tumour stage (P<0. 002), malignancy grade (P<0.007) and MDR-1 (P<0.03) were significant p rognostic variables for both survival and disease-free period. Lower M DR-1 expression was correlated with poorer prognosis. On multivariate analysis, MDR-1 and tumour stage were significant factors for predicti ng the disease-free period, whereas tumour stage and malignancy grade were the most relevant factors for survival time. Calculating prognost ic indices based on the results of the Cox analysis, MDR-1 could repla ce malignancy grade, resulting in a better prediction of survival and disease free period (P<0.001 vs 0.0031, P<0.001 vs 0.021, respectively ). Conclusion MDR-1, an established predictor for chemoresistance, may also be a potent prognostic factor for outcome in patients with local ly confined RCC. Moreover. MDR-1 expression seems to correlate with th e differentiation of the RCC and thus its value as an objective measur e of the degree of differentiation should be further explored.