ELEVATED SERUM LEVELS OF A C-ERBB-2 ONCOGENE PRODUCT IN OVARIAN-CANCER PATIENTS AND IN PREGNANCY

Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been show n to be a prognostic marker in ovarian cancer. In order to obtain furt her information on th biological role of the c-erbB-2 gene product p18 5 it is necessary to quantify expression levels. In this study we eval uate an enzyme-linked immunosorbant assay (ELISA) for the extracellula r domain of p185 to determine whether a soluble oncoprotein fragment c an be detected in the serum of ovarian cancer patients and in the seru m of pregnant women. Sera from 199 women (57 previously untreated ovar ian cancer patients, 62 pregnant women and 80 healthy controls) were a ssayed in a sandwich ELISA utilizing two mouse monoclonal antibodies. To study c-erbB-2 overexpression in ovarian cancer tissue samples we h ave used an immunohistochemical technique involving a monoclonal antib ody specifically reactive with the external domain of the protein p185 . The mean serum value for the normal controls was 1203 HNU/ml with a standard deviation (SD) of 279 HNU/ml and a range of 595-1947 HNU/ml. We chose a level of 1761 HNU/ml (2 SD above the mean) as a cut-off to distinguish individuals with elevated levels. The ovarian cancer patie nts' serum values ranged from 526 to 16 332 HNU/ml. Immunohistochemica lly detectable p185 was noted in 8 of 57 ovarian cancer patients. The oncoprotein fragment levels in the sera from these 8 patients ranged f rom 878 to 16 332 HNU/ml. Of 8 patients with p185 overexpression in th eir tumors, 4 had elevated serum levels. In the sera from the 49 cance r patients without overexpression the values were distributed in the r ange 526-2892 HNU/ml. There was no association between serum oncoprote in fragment levels and tumor stage, histological type or grading. Seru m concentrations of the p185. fragment in pregnancy ranged from 612 to 3265 HNU/ml. The highest levels were found in the third trimester. Th e results of the present study raise the possibility that the soluble c-erbB-2 protein level in serum is an indicator for cell proliferation and therefore deserves further evaluation as a diagnostic tool in ova rian cancer patients and pregnancy.