Immunohistochemical Expression of Cell-Cycle Proteins in Renal Cell Carcinoma and their Prognostic Significance
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- Category: Vol. 77, September 2009
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Immunohistochemical Expression of Cell-Cycle Proteins in Renal Cell Carcinoma and their Prognostic Significance, MAGDA H. BAKR, NEHAL S. ZAFER and NASHWA M. EMARA
Abstract
Molecular markers that predict prognosis more than stage and grade remain the elusive holy grail of renal cell carcinoma (RCC researchers). Many molecules have been identified, as a consequence of the elucidation of the molecular biology of RCC progression and metastasis, but few have remained significant above clinical and pathologic factors in multivariate analysis.
The goal of the study was to evaluate Immunohistochem-ical expression of the cell-cycle regulatory proteins p27(Kip1) and cyclin E in normal human kidneys and renal cell carcinoma (RCC) tissues. Association was analyzed with cancer clinical parameters.
Material and Methods: We have examined the protein contents of cyclin E and p27 in 57 cases of RCCs, using immunohistochemistry.
We found significantly increased expression of p27 in normal tissue relative to tumor (p=0.015). Low protein content of p27 was associated with high TNM stage, lymph node status and poor prognosis for patients with renal cell carcinoma. No significant association with grade, gender or age We further observed substantial differences in the pattern of G1/S regu-latory defects between the different RCC subtypes. The majority of both conventional and papillary cases expressed p27, however, chromophobe tumours generally showed low p27 staining.
Conversely, high expression of cyclin E was demonstrated in renal cell carcinoma tissue relative to normal kidney (p=0.027) and was associated with high nuclear grade and stage. No significant association with lymph node metastases, gender, age, tumor recurrence, death or survival. We further observed that papillary RCCs exhibited high cyclin E than other two subtypes.
In conclusion, this study shown that cyclin E as well as p27 were deregulated in renal cell carcinoma and that loss of p27(Kip1) expression is a risk factor for the disease recurrence and cancer-related patient death.