Association of high cytoplasmic expression of p27 Kip1 on cancer-specific survival in clear cell renal cell carcinoma.

Abstract

418 Background: p27Kip1 is considered to contribute to the progression of ccRCC and is targeted by next generation dual-therapies. Cytoplasmic and nuclear differences of p27 Kip1 expression and localization in benign and clear cell renal cell carcinoma (ccRCC) were analyzed with regard to overall survival (OS) and cancer-specific survival (CSS). Methods: In 140 patients, ccRCC and corresponding benign kidney tissue were analyzed for nuclear and cytoplasmic staining of p27Kip1 by immunohistochemistry using a tissue microarray technique. Staining intensity and percentage of positive stained cells are given as expression scores. p27Kip1 expression was categorized as high if ccRCC tissue stained stronger than the respective level of the corresponding benign tissue and categorized as low if ccRCC tissue stained less than or equal to the corresponding benign tissue. Differences in OS and CSS were analyzed by log-rank analysis and expression levels were correlated with tumour and patient characteristics using Fisher’s exact test. Results: Cytoplasmatic (mean [SD]: 13.8% [1.2%] vs 10.7% [1.7%]; P = 0.04) and nuclear (mean [SD]: 75.6% [2.7%] vs 13.6% [2.1%]; P < 0.001) staining of p27Kip1 were significantly stronger in ccRCC tissues compared to benign tissue. High cytoplasmic p27Kip1 expression was significantly associated with a higher T and N stage, Fuhrman grade and the presence of metastatic disease (P < 0.001). The median follow-up time was 38.2 months. There was no difference in OS between the low and high expression groups, although CSS was significantly lower in patients with high cytoplasmic p27Kip1 (P < 0.001) and CSS heavily tended to be lower in the nuclear low expression group (P = 0.069). Conclusions: High cytoplasmic p27Kip1 levels in renal cancer tissues are associated with advanced disease and reduced cancer specific survival, whereas low nuclear expression levels appear to be beneficial. The present study corroborates the consideration of cytoplasmic p27Kip1 for future diagnostic and targeted therapeutic approaches in RCC establishing a potential protective shift of p27Kip1 from the cytoplasm to the nucleus.