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Cancer Biother Radiopharm. 2004 Jun;19(3):331-42.

Predictive impact of retinoid X receptor-alpha-expression in renal-cell carcinoma.

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Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany.



Retinoid receptors are nuclear transcription factors that mediate the effects of retinoids on gene expression. In our study, we analyzed the expression of retinoid X receptor-alpha (RXR-alpha) and its prognostic value in renal-cell carcinoma (RCC) patients exhibiting stage IV disease upon first diagnosis or thereafter.


Detection of RXR-alpha was performed on tumor specimens from 63 patients with primary RCC, using immunohistochemical techniques. For our evaluation of the immunostaining results, we developed a new cell-counting system based on the subcellular distribution of immunoreactivity. The impact of the subcellular distribution of RXR-alpha on the prognosis of patients with RCC was analyzed statistically among other clinicopathologic factors. The primary end point was survival.


In 34 RCC samples (54.0%), RXR-alpha was detected predominantly in the nucleus, while 25 RCC specimens (39.7%) displayed an aberrant subcellular distribution pattern, with a predominantly cytoplasmic staining with nuclear sparing in 15 specimens (23.8%), and a combined nuclear and cytoplasmic staining in 10 specimens (15.9%). Very faint to undetectable immunoreactivity was noted in 4 cases (6.3%) of RCC. Univariate Kaplan-Meier analysis showed that patients with a predominantly nuclear localization of RXR-alpha had a significantly prolonged survival after primary tumor diagnosis, when compared to patients with a predominantly aberrant subcellular distribution profile (p < 0.01). Furthermore, multivariate analysis revealed that an aberrant subcellular distribution of RXR-alpha in RCC was an independent predictor of poor survival (p < 0.01).


Our study indicated that the subcellular intratumoral distribution pattern of RXR-alpha could independently predict the survival of RCC patients. However, the exact mechanisms underlying the aberrant compartmentalization and the functions of RXR-alpha in RCC remain to be determined.

[Indexed for MEDLINE]

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