Embryonic Stem Cell Factor Sox2 in Ovarian Carcinomas – Significant Association with More Poorly Differentiated Carcinomas and Longer Overall Survival in a Subgroup of Stage II-IV High-Grade Serous Carcinomas.
Annette Staebler, Deborah Pham, Veit Scheble, Petra Bareiss, Hans Neubauer, Claudia Lengerke, Sven Perner, Tanja Fehm. University of Tuebingen, Germany; University Hospital of Bonn, Germany
Background: The transcription factor Sox2 is involved in the maintenance of embryonic stem cell pluripotency and is expressed in several carcinoma types such as adenocacinoma of the lung and squamous cell carcinomas (SCC) of various origins. The gene SOX2 is located at chromosome 3q26, a region that is a frequently amplified in serous ovarian carcinoma. This study aims to explore the potential role of Sox2 in ovarian carcinogenesis by correlating Sox2 protein expression and gene amplification with different histological types of ovarian carcinomas, tumor grade and clinical outcome.
Design: 209 consecutive cases of ovarian carcinoma (149 serous, 38 endometrioid, 11 clear cell, 5 mucinous and 6 transitional cell carcinomas) were analyzed by immunohistochemistry in a tissue microarray for nuclear expression of Sox2. FISH analysis for gene amplification of SOX2 was performed for the serous carcinomas. Overall survival was compared by Kaplan-Meier Analysis
Results: 57% of all carcinomas showed detectable Sox2 positive cells with no significant difference between the major histological types (serous 58.4%, endometrioid 57.9%, clear cell 45.5%). Overall, Sox2 expression was more frequent in less differentiated tumors (G1: 38.9%, G3: 63.4%, p= 0.04). Low level gene amplification was detected in 22% of cases and did not correlate with gene expression levels. Surprisingly, analysis of the largest homogenous group (high-grade serous, stage II-IV) showed a favourable effect of Sox2 expression on overall survival (median 40 months vs. 25 months, p= 0.008).
Conclusions: Sox2-positive cells can be detected by immunohistochemistry in a majority of ovarian carcinomas, with increasing frequency in high-grade tumors. However, within the group of high grade serous carcinomas Sox2 expression is associated with a significantly better prognosis, suggesting that in this specific tumor entity activation of certain stemness-pathways may unexpectedly predict favourable outcome.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 9:00 AM
Platform Session: Section D, Monday Morning