Is the expression of multidrug resistance gene product a prognostic indicator for the clinical outcome of patients with renal cancer?
OBJECTIVE
To determine the significance of the expression of the multidrug resistance gene product (MDR-1) for the aggressiveness of renal cell carcinoma (RCC).


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).


CONCLUSIONS
MDR-1, an established predictor for chemo-resistance, 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.
Hofmockel
G
G
Department of Urology, University of Würzburg Medical School, Germany.
Bassukas
I D
ID
Wittmann
A
A
Dämmrich
J
J
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019450:Genes, MDR; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000401:mortality; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome