Receptors for hormones and growth factors and (onco)-gene amplification in human ovarian cancer.
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-I receptors (IGF-I-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 (1+). 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.
Berns
E M
EM
Division of Endocrine Oncology (Department of Medical Oncology), Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Klijn
J G
JG
Henzen-Logmans
S C
SC
Rodenburg
C J
CJ
van der Burg
M E
ME
Foekens
J A
JA
D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics; D001345:Autoradiography; D003600:Cytosol / Q000737:chemistry; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000235:genetics; D010053:Ovary / Q000737:chemistry*; D011519:Proto-Oncogenes; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D017451:Receptors, Somatomedin
D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D017451:Receptors, Somatomedin; D066246:ErbB Receptors