Prognostic significance of multidrug-resistance protein (MDR-1) in renal clear cell carcinomas: A five year follow-up analysis

Background: A large number of renal cancer patients shows poor or partial response to chemotherapy and the mechanisms have not been still understood. Multi-drug resistance is the principal mechanism by which many cancers develop resistance to chemotherapic drugs. The role of the multi-drug resistant transporter ( MDR-I/P-lycoprotein), the gene product of MDR-1, and that one of the so-called multi-drug resistance associated protein ( MRP), two energy-dependent efflux pumps, are commonly known to confer drug resistance. We studied MDR-1 expression in selected cases of renal cell carcinoma ( RCC),clear cell type, with long-term follow-up, in order to establish its prognostic role and its possible contribution in the choice of post-surgical therapy. Methods: MDR-1 has been studied by standard LSAB-HRP immunohistochemical technique, in paraffin embedded RCC samples. Protein expression has been compared to clinical and histopathological data and to disease specific survival of RCC patients, by Kaplan-Meier curve and Cox multivariate regression analyses. Results: Two groups of RCCs were obtained by esteeming MDR-1 expression and disease specific survival ( obtained with Kaplan-Meier curve and Cox multivariate regression analyses): the first one presents low or absent MDR-1 expression and good survival; the second one is characterized by high MDR-1 expression and significant poor outcome ( p < 0.05). Afterwards, we have found disease specific survival, adjusted for stages and independent of therapy: this difference of survival rates was statistically significant ( p < 0.05). Stage adjusted disease specific survival rate, according to MDR- 1 expression and therapy in patients affected by RCC in early stage ( stage I), has revealed that the group of patients with high MDR- 1 expression and without adjuvant therapy showed poor survival ( p < 0.05). Cox multivariate regression analysis has confirmed that, in our cohort of RCC ( clear cell type) patients, the strong association between MDR- 1 and worse outcome is independent not only of the adjuvant therapy, but also of the other prognostic parameters ( p < 0.05).