Expression Analysis of Newly Identified EMT Genes in High Grade Serous Carcinoma of the Ovary and Uterus.
Brian D McMillen, Ximing Yang, Jian-Jun Wei. Northwestern University, Chicago, IL
Background: The pathobiology of high-grade serous carcinoma (HGSC) of the ovary is currently not well understood, and is an area of active investigation. In a recent study, we identified a group of epithelial-mesenchymal transition (EMT) genes that are directly or indirectly regulated by the oncogene HMGA2 in ovarian surface epithelial (OSE) cells. To test whether HMGA2-mediated aggressive tumor growth in HGSC acts through regulation of EMT genes, we decided to examine whether these EMT genes are expressed in HGSC. These genes have never been studied in depth regarding the pathogenesis of ovarian tumors.
Design: Our study includes 96 serous tumors, including 56 ovarian high grade serous carcinomas (OSC), 18 serous borderline tumors (LMP) and 22 uterine serous carcinomas (USC). We examined HMGA2 and its target EMT gene expression, including ID1, LUM, POSTN, and STC2 by immunohistochemistry. Associated markers p53, ER, PR and Ki-67 were also included.
Results: In ovarian surface epithelial cells (OSE), four EMT associated genes (ID1, LUM, POSTN, and STC2) are regulated by HMGA2. In this study, we found that HMGA2 positive HGSC had significant down regulation of ID1, LUM and POSTN, and up regulation of STC2 in comparison to HMGA2 negative HGSC. The findings are consistent with our predictions based on gene expression in OSE cell lines. Importantly, we found HMGA2 and its EMT genes are positively associated with lymph node metastasis, suggesting an increased propensity towards aggressive behavior in tumors expressing these genes. There was significant difference of EMT gene expression between tumor cells and surrounding stroma. Lastly, HGSC from both ovary and uterus showed a very similar gene expression pattern.
Conclusions: HMGA2 and its associated EMT genes are significantly dysregulated in HGSC and they are positively correlated with lymph node metastases. Differential expression of these EMT genes between tumor cells and surrounding stroma suggests a functional role in aggressive tumor growth in HGSC. In particular, distinct expression patterns of these EMT genes in HGSC may provide novel markers for the study of HGSC.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 102, Tuesday Afternoon