Published in Cancer Detection and Prevention 1997; 21(6):532-539.

Immunohistochemical Assessment of Proliferation Markers and Altered Gene Expression in Archival Specimens of Ovarian Epithelial Tumors

Mahmoud A Khalifa MD PhD FRCPCa, David A Lacher MDb, Janice M Lage MDb, Robert S Mannel MDc, Joan L Walker MDc, Lee H Angros MSd, Kyung-Whan Min MDd

aDepartment of Pathology, Memorial University of Newfoundland, Saint John's, Canada; bDepartment of Pathology, Georgetown University, Washington, DC; and Departments of cGynecologic Oncology and dPathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK

Address all correspondence and reprint requests to: Mahmoud A. Khalifa, M.D., Ph.D., F.R.C.P.(C.), Department of Pathology, Memorial University of Newfoundland. The General Hospital, Saint John's, Newfoundland, AlB 3V6, Canada.

ABSTRACT: Recently reported morphologic and molecular genetic evidence suggests that some ovarian carcinomas arise from their benign and low malignant potential (LMP) counterparts. In order to help reach a better understanding of ovarian tumorigenesis, we studied a wide range of gene products involved in cellular growth regulation in archival material obtained from three groups of tumors with graduated malignant potential. Immunohistochemical staining was performed for Ki-67, proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), HER-2/neu-encoded receptor protein. p53 gene product. and multidrug resistance gene product (P-glycoprotein). The expression of EGFR, HER-2/neu-encoded receptor protein. and mutant p53 product was significantly lower in LMP tumors than in carcinomas (p < 0.05). HER-2/neu immunopositivity was more prevalent in adenocarcinomas than in LMP tumors, and the proportion of HER-2/neu-positive adenocarcinomas increased with the progression of the disease. The staining differences between LMP tumors and adenocarcinomas with antibodies against Ki-67, PCNA, and P-glycoprotein were not statistically significant. Immunohistochemical detection of EGFR, HER-2/neu, and p53 in ovarian epithelial tumor is relevant to ovarian tumorigenesis. It could serve as a powerful tool for the pursuit of retrospective studies focused on these important biologic markers.

KEY WORDS: borderline tumors, low malignant potential tumors, oncoproteins, ovarian neoplasms, proliferation markers, protooncogenes.