Role of EZH2 in Ovarian Carcinogenesis
S Bandyopadhyay, A Sood, AR Munkarah, MH Arabi, H Guan, K Hayek, R Ali-Fehmi. WSU/KCI/DMC, Detroit, MI; MDACC, Houston, TX; Wayne State University/Henry Ford Hospital System, Detroit, MI
Background: Despite efforts to improve outcome in patients with ovarian cancer, it remains the leading cause of death from gynecologic malignancy. Therefore, new targets for therapeutic development are needed. The aim of the study was to evaluate the significance of a novel transcriptional repressor, enhancer of Zeste 2 (EZH2), in patients with ovarian cancer via immunohistochemistry (IHC).
Design: The departmental archives were searched and 209 patients diagnosed with epithelial ovarian neoplasms (between 1992 and 2002) were included in the study. Cases were reviewed by a gynecologic pathologist and tissue micro-array sections were stained for Cyclooxygenase-1 (COX-1), Cyclooxygenase -2 (COX-2), EZH2, glucose transporter-1 (GLUT-1), VEGF-1 and VEGF-R by immunohistochemistry. The expression of these proteins was scored as low and high based on intensity and percentage of positive cells. Patients' characteristics and follow-up were obtained from the database of the division of gynecologic oncology. The stage (I-IV), grade (borderline, low grade and high grade) and histologic type (serous and non-serous) was also noted. Statistical analysis was performed using Pearson Chi square and Spearman correlation test. Survival analysis was done using Kaplan Meier curves and log rank test.
Results: The average age of the patients was 57.7 years (range 24-89 years), 145 had high stage (III and IV), 140 had high grade, and 164 had serous histology. High levels of EZH2 expression correlated with stage, serous histology and high tumor grade. Patients with high levels of EZH2 expression had significant (p=0.028) shorter progression free survival (PFS, 88 months) and overall survival (OS, 92 months) compared to low expression (PFS 157 months) and (OS 157 months). Significant positive correlation was observed between expression of EZH2 and the expressions of several proteins involved in angiogenesis and metastasis such as COX-1, COX-2, GLUT-1, iNOS and p53 (r=0.41 ,p<0.001 ).
Conclusions: EZH2 warrants further investigation as a potential marker for targeted therapy given its prognostic significance and association with COX-1, COX-2 and GLUT-1.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 158, Wednesday Morning