Clinical Significance of HER-2/neu Oncogene Amplification Detected by Differential PCR in Advanced Human Ovarian Cancers

Ryu, S Y; Kang, S B

Abstract

The HER-2/neu oncogene, located on chromosome 17q, encodes a transmembrane cell surface glycoprotein of 185kD that is similar to the epidermal growth factor receptor. HER-2/neu oncogene amplification was shown to occur in a number of adenocarcinomas and seems to be a valuable prognostic parameter. This present study was carried out to investigate the prevalence of HER-2/neu oncogene amplification by differential polymerase chain reaction and to examine whether HER-2/neu oncogene overamplification has any prognostic significance in advanced ovarian cancer patients. Amplification of HER-2/neu oncogene was assessed in 32 cases of FIGO stage III and IV advanced ovarian cancers (24 epithelial ovarian cancers, 2 Brenner tumors, 2 malignant mixed mullerian tumors, 2 granulosa cell tumors, 1 struma ovarii, 1 Krukenberg tumor) using differential polymerase chain reaction. HER-2/neu oncogene was amplified in all of the ovarian cancers (100%, 32/32), but significant overamplification[gene copy number > or = 1.5 a.u. (arbitrary unit)] was assessed in 50% (12/24) of epithelial ovarian cancers. There was no correlation between HER-2/neu oncogene overamplification and cell type or grade of tumor or initial CA-125 level. The clinical complete remission rate in high copy group (gene copy number > or = 1.5 a.u.) was 25% (3/12) and that of low copy group (gene copy number < 1.5 a.u.) was 50% (6/12), and pathologic complete remission rate was 0% (0/12) in high copy group and 25% (3/12) in low copy group. Median survival in high copy group was 28 months and 35 months in low copy group, and there was no correlation between HER-2/neu oncogene overamplification and overall survival (p=0.12). This result suggests that HER-2/neu oncogene overamplification is not a significant prognostic factor of advanced ovarian cancer, but large scaled prospective randomized studies are required.