Receptors for hormones and growth factors and (ONCO)‐gene amplification in human ovarian cancer

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Abstract
Receptor status and gene amplification were studied in advanced human ovarian adenocarcinoma tissues, borderline and benign ovarian tumours and normal ovarian tissues. Sixty‐five percent (53/82) of ovarian adenocarcinomas, 57% (8/14) of benign/borderline tumours and only 31% (5/16) of normal ovarian tissues studied showed specific 125I‐EGF (epidermal growth factor) binding (median: 17; 10; and 0 fmol EGF‐R/mg protein, respectively) and a significant increase in progesterone receptor (PgR) levels was observed in these groups (median: 5; 33; and 152 fmol/mg protein, respectively). No correlations were observed between the levels of EGF‐R and the levels of either oestrogen receptors (ER) or PgR. All membrane samples of 25 adenocarcinomas studied by Scatchard analysis were positive for insulin‐like growth‐factor‐1 receptors (IGF‐1 ‐R) and contained higher IGF‐I‐R levels than membranes of 10 normal ovarian tissues, of which 9 were positive (median: 64 and 26 fmol IGF‐I‐R/mg membrane protein, respectively). Also, as measured by autoradiography, 37 adenocarcinoma tissues showed a higher expression of IGF‐I‐R (1.5+ to 4+) than sections derived from 10 normal ovarian tissues (I +). 125I‐IGF‐I binding was predominantly associated with epithelial tumour cells, the surrounding connective tissue was negative and in several samples high expression of IGF‐I‐R was found in areas of tumour necrosis. Southern blot analysis of DNAs isolated from 25 ovarian adenocarcinomas revealed no amplification of the IGF‐I ‐R or the EGF‐R gene. The HER2/neu gene was amplified only in 2 out of 3 histologically confirmed endometrioid adenocarcinomas studied but not in 22 other tumours. An amplification of the c‐myc gene was observed in 28% (7/25) of the tumours. All c‐myc‐amplified tumours were PgR‐negative. No rearrangement was observed for any of the genes studied. In conclusion, ovarian adenocarcinoma tissues show a decrease in PgR levels and an increased expression of IGF‐I‐R and EGF‐R, in the absence of gene amplification, when compared to benign/borderline ovarian tumours and normal ovarian tissues. In addition, amplification of the c‐myc and HER2/neu genes, without rearrangement of these genes, occurs in a minority of these tumours.