Prognostic significance of multidrug-resistance protein MDR-1 in renal clear cell carcinomas: A five year follow-up analysisReport as inadecuate




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BMC Cancer

, 6:293

First Online: 19 December 2006Received: 15 September 2006Accepted: 19 December 2006DOI: 10.1186-1471-2407-6-293

Cite this article as: Mignogna, C., Staibano, S., Altieri, V. et al. BMC Cancer 2006 6: 293. doi:10.1186-1471-2407-6-293

Abstract

BackgroundA 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.

MethodsMDR-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.

ResultsTwo 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.

ConclusionIn 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.

List of abbreviationsRCCrenal cell carcinoma

MDR-1-P-glycoproteinmulti-drug resistant transporter

VEGFRvascular endothelial growth factor receptor

MRPmulti-drug resistance associated protein

MVAmultivariate regression analysis

LSAB-HRPlinked streptavidin-biotin horseradish peroxidase

DAB3,3-diaminobenzidine.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-6-293 contains supplementary material, which is available to authorized users.

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Author: Chiara Mignogna - Stefania Staibano - Vincenzo Altieri - Gaetano De Rosa - Giuseppe Pannone - Angela Santoro - Rosanna Zamp

Source: https://link.springer.com/







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