RASSF1A protein expression and correlation with clinicopathological parameters in renal cell carcinoma

Hossein Tezval,Jürgen Serth,Stefan Machtens,Ira Matuschek,Axel S Merseburger,Markus A Kuczyk

doi:10.1186/1471-2490-8-12

Hossein Tezval, Jürgen Serth + Show 4 more

Open Access

https://doi.org/10.1186/1471-2490-8-12

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Abstract

BackgroundEpigenetic silencing of RAS association family 1A (RASSF1A) tumor suppressor gene occurs in various histological subtypes of renal cell carcinoma (RCC) but RASSF1A protein expression in clear cell RCC as well as a possible correlation with clinicopathological parameters of patients has not been analyzed at yet.Methods318 primary clear cell carcinomas were analyzed using tissue microarray analysis and immunohistochemistry. Survival analysis was carried out for 187 patients considering a follow-up period of 2–240 month.ResultsExpression of RASSF1A was found to be significantly decreased in tumoral cells when compared to normal tubular epithelial cells. RASSF1A immunopositivity was significantly associated with pT stage, group stage and histological grade of tumors and showed a tendency for impaired survival in Kaplan-Meier analysis.ConclusionWhile most tumors demonstrate a loss of RASSF1A protein, a subset of tumors was identified to exhibit substantial RASSF1A protein expression and show increased tumor progression. Thus RCC tumorigenesis without depletion of RASSF1A may be associated with an adverse clinical outcome.

Highlights

Epigenetic silencing of RAS association family 1A (RASSF1A) tumor suppressor gene occurs in various histological subtypes of renal cell carcinoma (RCC) but RASSF1A protein expression in clear cell RCC as well as a possible correlation with clinicopathological parameters of patients has not been analyzed at yet
Specific immunopositivity for RASSF1A was exclusively observed in the cytoplasm of tumor and normal tubular epithelial cells [7]
Positivity of RASSF1A was found to be significantly decreased in tumoral cells when compared to normal tubular epithelial cells (p < 0.001, paired t-test)

Summary

Introduction

Epigenetic silencing of RAS association family 1A (RASSF1A) tumor suppressor gene occurs in various histological subtypes of renal cell carcinoma (RCC) but RASSF1A protein expression in clear cell RCC as well as a possible correlation with clinicopathological parameters of patients has not been analyzed at yet. Clear cell renal cell carcinoma (CC-RCC) as the most frequent subtype of RCC has been described to demonstrate loss and/or alteration of chromosome 3p [1,2]. Some tumor suppressors and candidates have been identified on 3p, such as FHIT at 3p14.2, VHL at 3p25 and the RAS association domain family 1A gene (RASSF1A) at. RASSF1A has been detected to undergo promoter hypermethylation and epigenetic silencing in CC-RCC [37]. The RASSF1A protein contributes to cell cycle control, stabilization of microtubules, cellular adhesion and motility [8]. Depletion of RASSF1A is associated with (page number not for citation purposes)

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