Phosphorylated FKHR Is Associated with Serous Neoplasia of the Ovary but Not with Mucinous Tumors
M Schumann, B Karberg, J Behm, O Buchweitz, A Staebler. University of Tuebingen, Tuebingen, Germany; University of Muenster, Muenster, Germany
Background: The Phosphatidyl-inositol 3-kinase (PI3K)- p-Akt signal transduction pathway has been implicated in ovarian carcinogenesis by several studies based on in-vitro experiments and the genomic gains in the region of chromosome 3q26. Furthermore elements of this pathway are particularly interesting as potential therapeutic targets. Therefore, this study aims at correlating the expression and activation of individual components of this pathway with different histological types of ovarian epithelial neoplasia.
Design: 231 cases of epithelial ovarian neoplasms of different histological type and grade were analyzed by immunohistochemistry in a tissue microarray for expression of p110alpha PI3K), phospho-Akt, mTOR and pFKHR. Clinical follow up was available in 64 cases of advanced serous carcinoma (max. 114 months, median 30 months after time of operation).
Results: The most significant difference between the individual groups was found for pFKHR. This component was detected in at least moderate staining in 53% of all serous carcinomas (n=96), 43% of serous borderline tumors (n=37) and 25 % of serous adenomas (n=12) but only in 10% of mucinous carcinomas (n=10) and in none of the mucinous borderline tumors (n=14) or adenomas (n=13). All other components were expressed in varying amounts in borderlinetumors and carcinomas, but no specific pattern was observed. Furthermore, pFKHR was associated with a shorter overall survival in patients with advanced stage serous carcinoma (34 vs 58 months, p= 0,028).
Conclusions: Expression of phosphorylated FKHR is associated with development of serous neoplasia of the ovary both of low-grade and high grade neoplasms. It does not seem to be involved in mucinous neoplasia which mostly relies on other signaltransduction pathways (eg. involving p42/44 MAPK). Expression of pFKHR also has a significant influence on overall survival of patients with advanced stage serous carcinoma of the ovary. It remains to examine the relevance of this parameter in lager independent patient collectives.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 144, Wednesday Morning