Reduced Expression of the Cell Cycle Regulator p27^Kip1 within the Invasion Front of Renal Cell Carcinomas Proved to be a Significant Marker for Disease-specific Survival

Abstract

Background: The expression of the negative cell cycle regulator p27^Kip1 is frequently found to be deregulated in various human cancer types. Whether the expression of p27^Kip1 can be used as a prognostic marker for renal cell cancer patients still remains to be clarified. Therefore, in the present investigation the expression of protein within different tissue areas obtained from renal cell carcinomas, their invasion front and corresponding histologically benign renal parenchyma was determined and statistically correlated with several tumor and patient characteristics including the disease-specific long-term survival following surgical treatment. Patients and Methods: For analysis of p27^Kip1 expression in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising 1260 tissue samples each obtained from the tumor itself, the invasive front as well as the non-malignant surrounding parenchyma. A sufficient follow-up after surgical therapy was available in 251 cases In total, 88 out of 251 patients (35%) had died from tumor progression after a median follow-up of 138 (36-240) months. Results: In univariate survival analysis, decreased expression of p27^Kip1 within tissue cores obtained from the invasion front was significantly correlated with the patients' disease-specific long-term survival (p=0.02, log rank test). In contrast, expression of p27^Kip1 within the primary tumors was not identified to reveal any prognostically important information. In Cox regression analysis, histological stage and grade (p<0.01), the presence of regional lymph node (p<0.01) or distant metastases at the time of surgery (p<0.01) as well as decreased expression of p27^Kip1 (p=0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery. Conclusion: Our analysis demonstrated that p27^Kip1 is heterogeneously expressed in renal cell carcinomas. Moreover, the results of the present study supports the prognostic value of p27^Kip1 protein expression for patients diagnosed with renal cell carcinoma.