Renal cell carcinoma (RCC) is notoriously resistant to a wide spectrum of treatment modalities such as radiation and chemotherapy. This has forced clinical researchers to look elsewhere for effective therapies for patients, such as immunotherapy and now, targeted therapy approaches. Little is known about the mechanism of chemoresistance by which RCC can escape the cytotoxic effects of chemotherapy. Here, Mignona and colleagues examine the multi-drug resistance gene (MDR-1) as a marker of prognosis and potential mechanism for chemoresistance in RCC.

Thirty tumor specimens of clear cell RCC from 30 patients were examined for MDR-1 expression using immunohistochemical techniques. MDR-1 is a membrane protein that is thought to facilitate excretion of chemotherapy molecules out of the cell. It was found to be expressed normally on the proximal renal tubule. With a mean follow-up of 69.8 months, 9 patients have died of RCC. The authors found that elevated MDR-1 expression was associated with a worse prognosis and increased likelihood of death from RCC (p less than 0.05). Focusing exclusively on Stage I patients, the authors found the addition of adjuvant vinblastine therapy improved outcome and that elevated levels of MDR-1 expression was associated with a poor prognosis in this group, independent of adjuvant therapy use.

MDR-1 expression is associated with a poor prognosis and increased likelihood of death from RCC. MDR-1 over expression may explain the chemoresistance phenotype that characterizes RCC.

Chiara Mignogna, Stefania Staibano, Vincenzo Altieri, Gaetano De Rosa, Giuseppe Pannone, Angela Santoro, Rosanna Zamparese, Massimino D'Armiento, Romualdo Rocchetti, Ernesto Mezza, Mario Nasti, Viviana Strazzullo, Vittorino Montanaro, Massimo Mascolo, and Pantaleo Bufo

BMC Cancer. 2006; 6: 293

By Christopher G. Wood, MD

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