COEXPRESSION OF THE HER-2 GENE-PRODUCT, P185(HER-2), AND EPIDERMAL GROWTH-FACTOR RECEPTOR, P170(EGF-R), ON EPITHELIAL OVARIAN CANCERS AND NORMAL-TISSUES

Monoclonal antibodies (MAbs) and immunoconjugates reactive with differ ent antigens expressed by neoplastic cells can inhibit tumor growth. U se of these agents in combination with one another or with chemotherap y can exert additive or synergistic cytotoxicity against tumor cells. An augmented therapeutic activity with favorable therapeutic index mig ht be attained when coexpression is observed on tumor cells, but not i n normal I:issues, In this study frozen sections of 19 ovarian cancers (2 stage I, 10 stage III, 2 stage IV, and 5 recurrrent), as well as 2 9 normal tissues, were evaluated by immunohistochemistry using 11 dist inct MAbs against :HER-2/p185 and 2 antibodies against EGF-R/p170 to a ssess coexpression of these receptors, HER-2/p185 expression was detec ted in 5 to 100% of ovarian cancers and 0 to 50% of normal ovarian epi thelia, depending ion the antibody used. EGF-R/p170 expression was det ected in approximately 70% of cancers and 40% of nor:mal ovaries by bo th antibodies. Coexpression of p185 and p170 was observed in 47-68% of ovarian cancers;and 9-18% of normal ovarian epithelial specimens depe nding upon the combination of antibodies used. Staining of 273 specime ns from 29 normal tissues indicated that coexpression of HER-2 and EGF -R is rare. Normal tissues that coexpressed both receptors in greater than or equal to 50% of the cases included cervix, endometrium, esopha gus,;skin, and prostate. These data confirm that HER-2 and EGF-R are m ore frequently expressed in advanced ovarian cancers than in normal ov arian epithelium and a significant fraction of these tumors coexpress both HER-2 and EGF-R.