Heterogeneous p27^Kip1 expression within primary renal cell cancers, their invasive margins and peritumoral renal parenchyma correlation with pathological and prognostic features

Introduction: The expression of the negative cell cycle regulator p27 ^Kip1 is frequently found to be deregulated in various human cancer types. Whether expression of p27^Kip1 can be used as prognostically relevant biological variables for renal cell cancer patients still remains to be clarified. Therefore, in the present investigation the expression within different tissue areas obtained from renal cell carcinomas was determined. Patients and Methods: For analysis of p27^Kip1 in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising of 1,260 tissue samples each obtained from the tumor itself, the invasive front as well as non-malignant surrounding parenchyma. A sufficient follow-up after surgical therapy was available in 251 cases. 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 protein 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 result of the present study supports the prognostic value of p27^Kip1 protein expression for patients diagnosed with renal cell carcinoma.