The expression of EGF receptors, EGF-like factors and c-myc in ovarian and cervical carcinomas and their potential clinical significance.
The expression of the epidermal growth factor receptor (EGF-R) and the c-myc oncogene was investigated in different specimens of ovarian and cervical carcinomas. The EGF-Rs were analyzed by EGF binding assay, immunohistochemistry and Northern blotting. For analysis of c-myc expression, we used Northern blotting and immunohistochemistry. Furthermore, tissue concentrations of EGF-like factors (EGF-F) were measured in the same tumor and non-malignant specimens. The biochemical determination of EGF-R demonstrated that EGF specific binding sites were detected in 36% of ovarian (n = 140) and 81% of cervical carcinomas (n = 42). High amounts of EGF-R (greater than 10 fmol/mg specific binding) were found in 8% of the ovarian and 41% of the cervical carcinomas. Increased expression of EGF-R specific mRNA was detectable in 7/21 ovarian and in 5/7 cervical carcinomas. A positive correlation between the amounts of EGF-R mRNA, the EGF-R binding data and the staining index of EGF-R immunohistochemistry was found. The EGF-R immunohistochemistry demonstrates that only the tumor cells produce increased amounts of EGF-R, while the stromal cells are EGF-R negative. Low amounts of EGF-R specific mRNA were also detected in biochemically EGF-R negative tumors. The c-myc specific mRNA signal was found in all cases investigated. It is shown that the c-myc expression was increased in 10/21 ovarian and 5/7 cervical carcinomas. There was no positive correlation between the amounts of EGF-R and c-myc mRNAs. The product of myc, as detected by immunohistochemistry, is found in tumor as well as in stromal cells. The levels of EGF-F were measured in extracts of 63 ovarian and 12 cervical carcinomas and in 21 non-malignant tissues. About 30% of the tumor extracts contained higher EGF-F levels (4-15 ng/mg) than those found in the non-malignant specimens. Tumors with high EGF-F levels expressed high amounts of c-myc RNA. The EGF-R status (n = 111) and the EGF-F levels (n = 63) were related to the prognosis of survival for patients with ovarian carcinomas. EGF-R positive (EGF-R(+)) ovarian carcinomas had a significantly higher response rate to chemotherapy. The survival time of the EGF-R(+) group is reduced compared to the EGF-R negative (EGF-R(-)) group if only patients in remission are used to construct survival curves. Furthermore, a poor prognosis for survival was noticed for ovarian carcinoma patients with high EGF-F levels.
Kohler
M
M
Institut für Biologie, Universität Freiburg, F.R.G.
Janz
I
I
Wintzer
H O
HO
Wagner
E
E
Bauknecht
T
T
D014408:Biomarkers, Tumor / Q000032:analysis*; D015152:Blotting, Northern; D004815:Epidermal Growth Factor / Q000032:analysis* / Q000235:genetics; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D010051:Ovarian Neoplasms / Q000032:analysis* / Q000473:pathology; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D012016:Reference Values; D002583:Uterine Cervical Neoplasms / Q000032:analysis* / Q000473:pathology
D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases