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

Chiara Mignogna¹ , Stefania Staibano¹ , Vincenzo Altieri² , Gaetano De Rosa¹ , Giuseppe Pannone³ , Angela Santoro³ , Rosanna Zamparese³ , Massimino D'Armiento⁴ , Romualdo Rocchetti² , Ernesto Mezza¹ , Mario Nasti¹ , Viviana Strazzullo¹ , Vittorino Montanaro² , Massimo Mascolo¹ and Pantaleo Bufo³

¹Department of Biomorphological and Functional Sciences, Section of Pathology, University of Naples "Federico II", Naples, Italy

²Department of Surgical Sciences, Section of Urology, University of Naples "Federico II", Naples, Italy

³Department of Surgical Sciences, Section of Anatomic Pathology and Cytopathology University of Foggia, Foggia, Italy

⁴Department of Surgical Sciences, Section of Urology, University of Naples "S.U.N.", Naples, Italy

author email corresponding author email

BMC Cancer 2006, 6:293doi:10.1186/1471-2407-6-293


Published:	19 December 2006

Abstract

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-1/P-glycoprotein), 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).

Conclusion

In our opinion, the results of this study well prove the relationship between MDR-1 expression and worse clinical prognosis in RCC, because MDR-1 over-expressing RCCs can be considered a group of tumours with a more aggressive behavior. This finding outlines a possible role of MDR-1 as prognostic factor, dependent and independent of multidrug resistance. These results could be useful to predict cancer evolution and to choose the appropriate treatment: this is another step that can stimulate further promising and interesting investigations on broader study population.