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

Tezval H, Merseburger AS, Matuschek I, Machtens S, Kuczyk MA, Serth J - BMC Urol (2008)

Bottom Line: Survival analysis was carried out for 187 patients considering a follow-up period of 2-240 month.Expression of RASSF1A was found to be significantly decreased in tumoral cells when compared to normal tubular epithelial cells.Thus RCC tumorigenesis without depletion of RASSF1A may be associated with an adverse clinical outcome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, Medizinische Hochschule Hannover, Hannover, Germany. tezval.hossein@mh-hannover.de

ABSTRACT

Background: 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.

Methods: 318 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.

Results: Expression 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.

Conclusion: While 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.

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Kaplan-Meier analysis and Hazard Plot. Hazard plot illustration of Kaplan-Meier analysis. Disease specific survival of patients demonstrating either low (< 25% immunopositively stained tumor cells) or high immunopositivity (> 25%) is shown. Borderline significance was obtained using log rank test analysis (p = 0.054).
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Figure 3: Kaplan-Meier analysis and Hazard Plot. Hazard plot illustration of Kaplan-Meier analysis. Disease specific survival of patients demonstrating either low (< 25% immunopositively stained tumor cells) or high immunopositivity (> 25%) is shown. Borderline significance was obtained using log rank test analysis (p = 0.054).

Mentions: Using a cut-off value of 25% for the relative amount of cells positively stained for RASSF1A in primary tumor specimens, as suggested by the labeling index (fig. 1) to allow discrimination of low and high positivity tumors, a disease-specific survival analysis was performed. Increased positivity of RASSF1A in the tumor samples demonstrated a tendency towards decreased survival in Kaplan-Meier analysis with border line significance (p = 0.054, log rank test), (fig. 3). Using RASSF1A immunopositivity as a continuous variable and Cox regression for survival analysis RASSF1A was not identified as a significant parameter (p = 0.239, hazard ratio = 1.005, 95% CI 0.997–1.013).


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

Tezval H, Merseburger AS, Matuschek I, Machtens S, Kuczyk MA, Serth J - BMC Urol (2008)

Kaplan-Meier analysis and Hazard Plot. Hazard plot illustration of Kaplan-Meier analysis. Disease specific survival of patients demonstrating either low (< 25% immunopositively stained tumor cells) or high immunopositivity (> 25%) is shown. Borderline significance was obtained using log rank test analysis (p = 0.054).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2572051&req=5

Figure 3: Kaplan-Meier analysis and Hazard Plot. Hazard plot illustration of Kaplan-Meier analysis. Disease specific survival of patients demonstrating either low (< 25% immunopositively stained tumor cells) or high immunopositivity (> 25%) is shown. Borderline significance was obtained using log rank test analysis (p = 0.054).
Mentions: Using a cut-off value of 25% for the relative amount of cells positively stained for RASSF1A in primary tumor specimens, as suggested by the labeling index (fig. 1) to allow discrimination of low and high positivity tumors, a disease-specific survival analysis was performed. Increased positivity of RASSF1A in the tumor samples demonstrated a tendency towards decreased survival in Kaplan-Meier analysis with border line significance (p = 0.054, log rank test), (fig. 3). Using RASSF1A immunopositivity as a continuous variable and Cox regression for survival analysis RASSF1A was not identified as a significant parameter (p = 0.239, hazard ratio = 1.005, 95% CI 0.997–1.013).

Bottom Line: Survival analysis was carried out for 187 patients considering a follow-up period of 2-240 month.Expression of RASSF1A was found to be significantly decreased in tumoral cells when compared to normal tubular epithelial cells.Thus RCC tumorigenesis without depletion of RASSF1A may be associated with an adverse clinical outcome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, Medizinische Hochschule Hannover, Hannover, Germany. tezval.hossein@mh-hannover.de

ABSTRACT

Background: 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.

Methods: 318 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.

Results: Expression 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.

Conclusion: While 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.

Show MeSH
Related in: MedlinePlus