High-Grade Serous Carcinoma of the Ovary: Negative but Highly Significant Correlation of PI3K Pathway Activation with Specific Chromosomal Aberrations
M Schumann, B Karberg, P Kuhlmann, J Behm, O Buchweitz, A Staebler. University of Tuebingen, Tuebingen, Germany; Ludwigsburg Hospital, Ludwigsburg, 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 and elements of this pathway serve as potential therapeutic targets. To elucidate the mechanism of activation and obtain information on potential alternative pathways, this study aims at correlating the activation of different components with specific chromosomal alterations in high-grade serous carcinoma.
Design: 114 cases of high grade serous carcinoma were analyzed by immunohistochemistry in a tissue microarray for expression of p110alpha PI3K, phospho-Akt, pmTOR and pFKHR. Corresponding chromosomal analysis by CGH was available for 85 cases.
Results: Unexpected results showed a significant but negative correlation between the activation of individual components of the PI3K-Pathway and the average number of chromosomal alteration (for example Pearson correlation: -0.278, p=0.009 for detection of pmTOR and -0.239 with p=0.028 for expression of PI3K(p110 alpha). Similar results were found with individual chromosomal alterations, that were negatively correlated with pathway activation: for example detection of pmTOR showed a significant inverse correlation with amplifications at chromosome 19q, losses of 4q and Xq (p= 0.004, 0.006 and 0.007). Interestingly, there were no positive correlations.
Conclusions: Expression and activation of individual components of the PI3K-pathway shows a negative but highly significant correlation with specific chromosomal alterations and is also reflected in a significantly lower number of overall aberrations. This finding suggests, that the entity of high-grade serous carcinomas consists of a broad spectrum of tumors, which are characterized by activation of signal-transduction pathways at one end, and increasing chromosomal instability at the other end.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 11:15 AM
Platform Session: Section D, Tuesday Morning