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

• Published in: BMC cancer 2006-12, Vol.6 (1), p.293-293, Article 293
• Main Authors: Mignogna, Chiara, Staibano, Stefania, Altieri, Vincenzo, De Rosa, Gaetano, Pannone, Giuseppe, Santoro, Angela, Zamparese, Rosanna, D'Armiento, Massimino, Rocchetti, Romualdo, Mezza, Ernesto, Nasti, Mario, Strazzullo, Viviana, Montanaro, Vittorino, Mascolo, Massimo, Bufo, Pantaleo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - physiology; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - physiology; Carcinoma, Renal Cell - diagnosis; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - mortality; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic - physiology; Humans; Kidney Neoplasms - diagnosis; Kidney Neoplasms - metabolism; Kidney Neoplasms - mortality; Male; Middle Aged; Prognosis; Survival Rate - trends
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-6-293

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. 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. 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). 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 canc