HER-2/neu Oncogene Amplification; A Factor for Predicting Response of Platinum-based Combination Chemotherapy in Ovarian Cancers

Kim, Yong Beom; Kim, Jae Weon; Park, Noh Hyun; Song, Yong Sang; Kang, Soon Beom; Lee, Hyo Pyo; Roh, Ju Won; Lee, Chul Min

Abstract

BACKGROUND: The HER-2/neu proto-oncogene (also known as c-ErbB-2) encodes a 185 kD transmembrane glycoprotein with intrinsic tyrosine kinase activity. Many studies revealed the correlation between the aberrant overexpression of HER-2/neu oncogene and poor prognosis of the malignant tumors such as breast, stomach, colon, lung cancers. But the significance of HER-2/neu oncogene overexpression as a prognostic factor in ovarian cancer remains controversial.
OBJECTIVE
The aims of this study were to assess the prevalence of HER-2/neu oncogene amplification by polymerase chain reaction(PCR) and to evaluate the prognostic significance of HER-2/neu oncogene overexpression in terms of chemo-responsiveness and survival rate.
MATERIALS AND METHODS
This study included 32 patients with advanced ovarian cancers(24 epithelial ovarian cancers, 2 Brenner tumors, 2 malignant mixed miillerian tumors, 2 granulosa cell tumors, 1 struma ovarii, 1 Krukenberg tumor). All patients had underwent staging laparotomy, and postoperative adjuvant chemotherapy with platinum-based combination chemotherapy. PCR was performed using tissues preserved in liquid nitrogen at the time of debulking operation. Overexpression of HER-2/neu oncogene was defined as being equal to or greater than 1.5 a.u. We analyzed whether the HER-2/neu overexpression correlated with chemoresponsiveness and 5-year survival rate(5-YSR). RESULT: HER-2/neu oncogene amplification was present in all of the ovarian cancers(32/32). Significant overexpression[gene copy number(GCN) > or =1.5 a.u.] was present in 13 of 32 ovarian cancers(41%) and 12 of 24 epithelial ovarian cancers (50%). The clinical response rate to chemotherapy in high copy group(GCN > or = 1.5 a.u.) was 67%(8/12) and that of low copy group(GCN<1.5 a.u.) was 92%(11/12)(p>0.05). Pathologic response rate to chemotherapy was 0%(0/5) and 50%(3/6), respectively(p>0.05). 5-YSR was 8% in high copy group and 25% in low copy group, but this difference was not statistically significant(p=0.17).
CONCLUSION
HER-2/neu overexpression might be a poor prognostic factor, but this difference was not definitely elucidated by satistical analytsis in this study. Larger scaled prospective randomized study is needed to define the prognostidc significance of the HER-2/neu overezpression in ovarian cancer.