Transcript Levels Of Aquaporin 1 And Carbonic Anhydrase Iv As Predictive Indicators For Prognosis Of Renal Cell Carcinoma Patients After Nephrectomy

Since failure of differentiation has been suggested to be involved in the neoplastic process and progression of tumors, we evaluated whether the transcript levels of differentiation markers of proximal renal tubular cells, from which renal cell carcinoma (RCC) arises, could be used as prognostic markers. We used Northern blot analysis to study the expression of aquaporin I (aqpI) and carbonic anhydrase IV (ca4) genes in 66 paired samples of primary RCC and non-tumorous kidney tissues. Poor differentiation of tumor cells and nonclear cell-subtype RCC were significantly associated with low levels of aqp I transcripts. When patients were divided into 2 groups according to level of aqp I transcript in RCC, a low level of aqpI was significantly associated with unfavorable outcome. Among 18 patients with metastatic RCC and 40 patients with moderately differentiated RCC, those with RCC expressing low levels of aqpI mRNA demonstrated poorer survival than those with RCC expressing relatively high levels of aqp I. Similarly, decreased expression of ca4 mRNA in RCC was associated with poor survival. On multivariate analysis, transcript levels of aqpI and stage of the tumor were the independent factors predicting disease-specific survival. Transcript levels of aqp I may serve as a new molecular prognostic marker in patients with RCC following nephrectomy. (C) 1998 Wiley-Liss, Inc.