Overexpression of EGFR Is a Poor Prognostic Indicator in Ovarian Cancer
B Djordjevic, DG Rosen, J Liu. M.D. Anderson Cancer Center, Houston, TX
Background: Epidermal growth factor receptor (EGFR) is a surface-bound receptor tyrosine kinase of the ErbB receptor family, which plays an important role in the control of cellular proliferation, differentiation and survival. EGFR signaling is dysregulated in a variety of solid tumors, and targeted therapy against EGFR is now available. Studies of EGFR expression in ovarian carcinoma to date have had variable results. The goal of this project is to characterize the expression of EGFR in different histologic types of ovarian carcinoma and evaluate EGFR as a prognostic marker.
Design: Samples from women who had primary epithelial ovarian carcinoma and had undergone initial surgery at our institution between 1990 and 2001 were identified and treatment and follow-up information was updated to June 2005 through review of medical records. Parameters recorded for each case included histological type, grade, stage, extent of debulking surgery, clinical response to platinum-based therapy, disease free interval (DFI) and overall survival (OS). Tissue microarrays were constructed and using 1mm cores. The immunohistochemical staining for EGFR was performed. EGFR staining was scored as 0 (no staining), 1+ (<20% of cells staining or faint staining), 2+ (20%-50% of cells staining or incomplete strong membrane staining) and 3+ (>50% cells staining with complete membrane staining). Differences in proportions were evaluated by chi square analysis. Disease survival rates were calculated using the Kaplan-Meier method and were compared using the log-rank test.
Results: 297 cases were identified comprising 240 serous, 33 endometrioid, 17 clear cell and 7 mucinous adenocarcinomas. Serous carcinomas showed a higher proportion of cases with high EGFR expression compared to endometrioid (p<0.05) and clear cell carcinoma (p<0.05). Patients with no clinical response to platinum-based therapy had higher levels of EGFR relative to those with partial response (p<0.05). A higher proportion of patients who did not have disease relapse had a negative to low expression of EGFR compared to patients that relapsed (p<0.05) or had progressive disease (p<0.05). Finally, patients with negative to low EGFR expression levels had better OS and DFI than patients with moderate to high expression.
Conclusions: High EGFR expression is a negative prognostic marker in ovarian carcinoma. In addition, overexpression of EGFR has a high association with serous ovarian carcinoma. These findings suggest that EGFR may be an important therapeutic target in ovarian carcinoma, and particularly in serous carcinoma.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 160, Wednesday Morning