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

Autor: Massimo Mascolo, Rosanna Zamparese, Giuseppe Pannone, E. Mezza, Vincenzo Altieri, C. Mignogna, Pantaleo Bufo, Vittorino Montanaro, Gaetano De Rosa, Viviana Strazzullo, Mario Nasti, Romualdo Rocchetti, Angela Santoro, Massimino D'Armiento, Stefania Staibano
Přispěvatelé: Mignogna, C, Staibano, Stefania, Altieri, V, DE ROSA, Gaetano, Pannone, G, Santoro, A, Zamparese, R, D'Armiento, Maria, Rocchetti, R, Mezza, E, Nasti, M, Strazzullo, V, Montanaro, V, Mascolo, Massimo, Bufo, P.
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Adult
Male
physiology
Humans
Kidney Neoplasm
Cancer Research
Drug resistance
lcsh:RC254-282
Surgical oncology
Renal cell carcinoma
Genetics
Carcinoma
Biomarkers
Tumor
80 and over
Carcinoma
Medicine
Humans
trends
Tumor Marker
ATP Binding Cassette Transporter
Subfamily B
Member 1
Carcinoma
Renal Cell
P-glycoprotein
Aged
Aged
80 and over
Neoplastic
biology
business.industry
diagnosis/metabolism/mortality
Female
Follow-Up Studies
Gene Expression Regulation
Cancer
Renal Cell
Middle Aged
medicine.disease
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Biological
Kidney Neoplasms
Adult
Aged
Aged
Multiple drug resistance
Gene Expression Regulation
Neoplastic
Survival Rate
biosynthesis/genetics/physiology
Oncology
diagnosis/metabolism/mortality
Male
Middle Aged
P-Glycoprotein
Immunology
biology.protein
Cancer research
biosynthesis/genetics/physiology
Prognosis
Survival Rate
Female
business
Clear cell
Research Article
Follow-Up Studies
Zdroj: BMC Cancer, Vol 6, Iss 1, p 293 (2006)
BMC Cancer
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: