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European Urology - p16INK4a Expression and Clinicopathologic Parameters in Renal Cell Carcinoma Show Comments PDF Print E-mail
  
Thursday, 01 March 2007
Volume 51, Issue 3, Pages 732-738 (March 2007)

Abstract -

Objectives:

The tumour suppressor gene p16INK4a is a cyclin-dependent kinase inhibitor, for which inactivation attributable to promoter hypermethylation or homozygous deletion has been described in malignancies. Little is known about p16INK4a protein levels in renal cell carcinoma (RCC) and its association with clinicopathologic parameters or disease progression.

Methods

The expression of the p16INK4a gene was analysed with the use of immunohistochemistry and tissue microarrays (TMA). Tissue cores were obtained from the primary tumour itself, the tumoural invasion front, and histologically benign peritumoural tissue of 397 nephrectomies. For statistical analysis, sections were classified into four groups according to the relative amount of positively stained cells: negative (0%), low (1–10%), intermediate (11–50%), and high positivity (>50%).

Follow-up data were analyzed for 198 patients (follow-up period: 2–240 mo; median: 138 mo).

Results

Absent or low expression of p16INK4a was observed in 82% of tumour samples. No statistically significant association was found between protein levels detected in tumour, invasion front, or normal renal tissues and any of the clinicopathologic variables. Survival analysis by Kaplan-Meier revealed a significant association between high expression (>50%) of p16INK4a in tumours and better disease-specific survival (p=0.03, log-rank test). Cox regression analysis showed that p16INK4a expression is an independent covariate in disease-specific survival (p<0.01).

Conclusions

The absence of p16INK4a expression in most tumour cells indicates that p16INK4a could be involved in the tumourigenesis of RCC. Immunohistochemically detected positivity for p16INK4a is a positive prognosticator for specific survival in both uni- and multivariate analyses.

Stephen O. Ikuerowo, Markus A. Kuczyk, Reinhard von Wasielewski, Olayiwola B. Shittu, Udo Jonas, Stefan Machtens, Jürgen Serth

Department of Urology, Medizinische Hochschule Hannover, Hannover, Germany
Department of Urology, Karl-Eberhards University, Tübingen, Germany
Department of Pathology, Medizinische Hochschule Hannover, Hannover, Germany
Division of Urology, University College Hospital and University of Ibadan, Ibadan, Nigeria

Accepted 8 August 2006 published online 24 August 2006.

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