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Is the expression of multidrug resistance gene product a prognostic indicator for the clinical outcome of patients with renal cancer?
Author(s) -
HOFMOCKEL G.,
BASSUKAS I.D.,
WITTMANN A.,
DÄMMRICH J.
Publication year - 1997
Publication title -
british journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 0007-1331
DOI - 10.1046/j.1464-410x.1997.00228.x
Subject(s) - malignancy , medicine , proportional hazards model , stage (stratigraphy) , univariate analysis , oncology , hazard ratio , survival analysis , cancer , log rank test , renal cell carcinoma , multivariate analysis , multiple drug resistance , disease , gastroenterology , drug resistance , biology , confidence interval , paleontology , microbiology and biotechnology
Objective To determine the significance of the expression of the multidrug resistance gene product (MDR‐1) for the aggressiveness of renal cell carcinoma (RCC). Patients and methods The study comprised 31 patients with clinically locally confined RCC treated with radical nephrectomy (mean age 64.1 years, range 41–78; mean follow‐up 5.4 years, range 4.3–7.3). Their survival time and disease‐free period were evaluated retrospectively. The expression of the MDR‐1 gene product was determined immunohistochemically using the JSB‐1 antibody in formalin‐fixed paraffin‐embedded tumour samples from these patients. The significance of this variable and tumour stage and malignancy grade was assessed for predicting the survival and disease‐free period using Kaplan‐Meier plots (log‐rank test or Tarone’s test) and the Cox multiple hazard regression analysis. Results In a univariate analysis, tumour stage ( P <0.002), malignancy grade ( P <0.007) and MDR‐1 ( P <0.03) were significant prognostic variables for both survival and disease‐free period. Lower MDR‐1 expression was correlated with poorer prognosis. On multivariate analysis, MDR‐1 and tumour stage were significant factors for predicting the disease‐free period, whereas tumour stage and malignancy grade were the most relevant factors for survival time. Calculating prognostic indices based on the results of the Cox analysis, MDR‐1 could replace malignancy grade, resulting in a better prediction of survival and disease‐free period ( P <0.001 vs 0.0031, P <0.001 vs 0.021, respectively). Conclusion MDR‐1, an established predictor for chemoresistance, may also be a potent prognostic factor for outcome in patients with locally confined RCC. Moreover, MDR‐1 expression seems to correlate with the differentiation of the RCC and thus its value as an objective measure of the degree of differentiation should be further explored.