February 22, 2007

P21 Is A Prognostic Marker For Renal Cell Carcinoma: Implications For Novel Therapeutic Approaches

UroToday.com- The identification and validation of molecular markers of prognosis are the future for renal cell carcinoma (RCC). Several molecules (carbonic anhydrase IX, the B7 family, etc.) have been identified that can predict patient outcome over and above current clinical staging paradigms, and also provide potential targets for future therapeutic intervention. The cell cycle protein p21 is involved in cell cycle and apoptosis regulation within the cell, and increased levels have been associated with adverse outcomes in many cancers, including breast cancer. Here, Weiss and the group from UCLA report on the prognostic significance of p21 expression, as detected by immunohistochemistry, in RCC.

Using a tissue microarray, the authors evaluated the expression of p21 on tissue samples from 366 patients with RCC. Some of the patients had matched primary tumors with metastatic lesions for comparative analysis. Overall, the authors report that the expression of p21 was highest in collecting duct carcinoma and lowest in oncocytoma. They also noted overall that there was increased expression of p21 in metastases relative to primary tumors. Within the large subset of patients with clear cell RCC, the authors found that increased expression of nuclear p21 was associated with a better prognosis in localized RCC. Conversely, in metastatic RCC, increased expression of both nuclear and cytosolic p21 was associated with a worse prognosis. The authors hypothesized that their data provided a rationale argument for the combination of DNA damaging agents with mTOR inhibitors in the treatment of metastatic RCC (but not localized RCC) due to the levels of p21 exhibited in the metastatic setting.

While the data presented here are preliminary and require further validation in other patient subsets, the results are interesting and provocative. They suggest a real divergence in the biology between metastatic RCC (where increased p21 expression was associated with a worse outcome) and localized RCC (where increased p21 was associated with a better outcome). This may have implications regarding the development of therapy for metastatic RCC that may have unpredictable results in the localized or locally advanced setting as an adjuvant.

Weiss RH, Borowsky AD, Seligson D, Lin PY, Dillard-Telm L, Belldegrun AS, Figlin RA, Pantuck AD
J Urol 17(1): 63-69, 2007

Reviewed by UroToday.com Contributing Editor Christopher G. Wood, MD, FACS

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