RAR-beta(1) overexpression in chromophobe renal cell carcinoma: a novel target for therapeutic intervention?

Aim: Retinoic acid (RA) has proven to possess modest but distinct activity in metastatic renal cell carcinoma (RCC), at least in a subgroup of patients. However, the exact molecular mechanisms leading to success or failure of RA application in individual patients are still unknown. As earlier studies have indicated that in RCC the RA receptor (RAR) beta might play a central role in RA signaling, we investigated the expression of the isoforms RAR-beta(1+2) in primary conventional and chromophobe RCC.

Methods: We used quantitative RT-PCR methodology to study RAR-beta(1) and RAR-beta(2) expression in ten primary conventional RCC samples (clear cell type), in two chromophobe RCC specimens, and the respective corresponding normal kidney tissues. The housekeeping genes RPS9 and RPLP0 were applied to normalize differences in mRNA quality and quantity.

Results: In contrast to conventional RCC samples, RAR-beta(1) was significantly overexpressed in both chromophobe tumors compared to the adjacent normal kidney tissue (p=0.03). On the contrary, RAR-beta(2) expression did neither differ significantly between conventional and chromophobe RCC (p=0.91) nor between malignant and normal kidney tissue (p>or=0.47).

Conclusion: We demonstrate for the first time a significant and specific overexpression of RAR-beta(1) in chromophobe RCC. In future we will have to confirm this result within a larger number of samples.