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14-3-3 Expression Is an Independent Prognostic Parameter for Poor Survival in Colorectal Carcinoma Patients

Authors' Affiliations: ¹ Tyrolean Cancer Research Institute; Departments of ² General and Transplant Surgery and ³ Hematology and Oncology, and ⁴ Institute of Pathology, University Hospital Innsbruck, Innsbruck, Austria

Requests for reprints: Albert Amberger, Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria. Phone: 43-512-570485-31; Fax: 43-512-570485-44; E-mail: albert.amberger{at}uklibk.ac.at.

Purpose: 14-3-3 is an intracellular, dimeric, phosphoserine binding protein that is expressed in epithelial cells and involved in cancer development. In this study, we examined the expression of 14-3-3 and evaluated its clinical significance in colorectal carcinoma.

Experimental Design: Expression of 14-3-3 was analyzed by Western blot in nine colorectal carcinoma cell lines, eight paired colorectal carcinoma tissues, and normal mucosas. Immunohistochemistry was used to evaluate expression of 14-3-3 in tissues of 121 colorectal carcinoma patients and to correlate it with clinical parameters.

Results: Western blot analysis of colorectal carcinoma cell lines and tissues revealed strong 14-3-3 expression in four of eight cell lines and 14-3-3 overexpression in carcinomas compared with normal mucosa in six of eight colorectal carcinoma tissue pairs. Immunohistochemical analysis revealed 14-3-3 overexpression in 38.8% of colorectal carcinoma samples. Furthermore, highly positive immunoreactivity was significantly correlated with tumor differentiation (P < 0.001) and pT stage (P < 0.003). In Kaplan-Meier analysis, 14-3-3 overexpression was associated with a significantly decreased survival time compared with negatively stained or low stained cases (P < 0.0096). In multivariate regression analysis, 14-3-3 expression emerged as a significant independent parameter (P < 0.037).

Conclusions: These results provide evidence that 14-3-3 expression increases during carcinoma progression in a subset of colorectal carcinoma. The overexpression of this antigen identifies patients at high risk. It is tempting to suggest that 14-3-3 overexpression either promotes tumor proliferation and/or prevents apoptotic signal transduction in colorectal carcinoma. Thus, targeting 14-3-3 might be a new therapeutic strategy in colorectal carcinoma.

Key Words: Immunohistochemistry • colon • cell lines • survival • prognostic parameter

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