p27KIP1-expression in human renal cell cancers: implications for clinical outcome.

BACKGROUND: p27Kip1 (p27) protein is an inhibitor of cyclin-dependent kinase complexes and prevents progression of cells from the G1- to the S-phase of the cell cycle. Decreased p27 expression has been shown to be associated with aggressive tumor behavior and decreased patient survival in numerous human malignancies. The aim of this study was to evaluate p27 expression in renal cell cancer and to assess its association with stage and grade as well as its relationship to patient outcome. MATERIALS AND METHODS: One hundred and fifty-four renal cell carcinoma specimens were evaluated for p27 expression by immunohistochemical staining. Immunohistochemical findings were correlated with tumor grade, tumor stage and patient outcome. RESULTS: A progressive loss of nuclear p27 expression was observed with increasing tumor grade. In poorly-differentiated tumors, p27 expression was significantly lower compared to well- and moderately-differentiated tumors (p = 0.025). p27 expression tended to decrease with increasing tumor stage, but the correlation was not statistically significant (p = 0.068). CONCLUSION: The present study suggests that renal cell carcinomas showed increased aggressiveness with loss of p27 expression. A longer follow-up period will demonstrate whether this cell cycle regulator will provide additional prognostic information in patients with renal cell carcinoma.

Distinct in vivo expression patterns of survivin splice variants in renal cell carcinomas.

Survivin, a novel member of the inhibitor of apoptosis protein (IAP) family, reduces the susceptibility of tumor cells to proapoptotic stimuli, thereby promoting tumor cell survival during tumor progression and treatment with anticancer drugs. Recently, we identified 2 novel alternative splice variants of survivin, survivin-2B and survivin-Delta Ex3, which differ in their antiapoptotic properties. Survivin-2B has lost its antiapoptotic potential and may act as a naturally occurring antagonist of antiapoptotic survivin and survivin-Delta Ex3. Because the in vivo expression of these splice variants in human cancer has not been analyzed so far, 57 renal cell carcinomas (RCCs) were explored using quantitative reverse transcriptase polymerase chain reaction. We found that all RCCs express survivin-Delta Ex3, survivin-2B and survivin, the latter being the dominant transcript. When we compared early and intermediate stages with late stages of clear cell RCCs, no significant changes in the expression levels of survivin and survivin-Delta Ex3 became evident. However, a significant decrease was observed for the mRNA ratio between survivin-2B and survivin in late tumor stages (p = 0.036). Chromophilic/papillary RCCs, which are known to be less aggressive than clear cell RCCs, did not show significantly lower expression levels of antiapoptotic survivin and survivin-Delta Ex3, compared with stage-adjusted clear cell RCCs. Our study demonstrates for the first time in vivo expression of functionally different survivin variants and suggests a role of these survivin splice variants in the progression and clinical behavior of human RCCs.