The prognostic value of cyclin D1 in renal cell carcinoma

Introduction

Renal cell carcinoma (RCC) is a family of distinct tumors, and a variety of molecules have been evaluated as prognostic markers for RCC. Cyclin D1, a cell cycle regulator, is overexpressed in several primary tumors.

Objective

To evaluate cyclin D1 expression as a prognostic marker in RCC.

Method

In total, 109 tumor specimens from patients with RCC were obtained from 2005 to 2010 at Hospital das Clínicas—Ribeirão Preto School of Medicine—USP, Brazil, and submitted to immunohistochemical analysis along with seven normal kidney tissue samples.

Results

All of the normal kidney samples lacked cyclin D1 immunohistochemical staining. In addition, there was lower protein expression in the papillary and chromophobe RCC samples. Patients with cyclin D1^low tumors (≤30 % positive cells) showed worse clinical outcome (p = 0.03), lower survival without metastasis and/or death by RCC (p = 0.03), high nuclear grade (p = 0.001), larger tumor size (p = 0.01), presence of symptoms at diagnosis (p = 0.04), necrosis (p = 0.004) and sarcomatoid morphology (p = 0.04). After multivariate analysis, cyclin D1 was not an independent significant factor for worse outcome; however, it improved the accuracy of the adopted prognostic system. The analysis performed for clear cell RCC alone showed similar statistical significance to that of the total cases.

Conclusions

Cyclin D1 protein was overexpressed in RCC. The types of RCC appear to exhibit different immunohistochemical staining patterns for cyclin D1; high protein expression was related to good clinical outcome and to most known favorable prognostic factors. Further investigations are necessary to reveal which mechanisms lead to cyclin D1 accumulation in neoplastic cells.