Amplification of the HER-2/neu Oncogene and Topoisomerase II-alpha by Chromogenic in Situ Hybridization in Breast Cancer.
- Author:
Ho Sung KIM
1
;
Beom Gyu KIM
;
Seong Jae CHA
;
Tae Jin LEE
;
Sung Jun PARK
;
Hyun Muck LIM
;
Sung Il PARK
Author Information
1. Department of Surgery, College of Medicine, Chung-Ang University, Seoul, Korea. kimbg0526@paran.com
- Publication Type:Original Article
- Keywords:
HER-2/neu;
Topoisomerase II-alpha;
CISH, Breast cancer
- MeSH:
Breast Neoplasms*;
Breast*;
Carcinoma, Ductal;
DNA Replication;
Drug Therapy;
Estrogens;
Gene Amplification;
Humans;
In Situ Hybridization*;
Lymph Nodes;
Neoplasm Metastasis;
Oncogenes*
- From:Journal of the Korean Surgical Society
2007;73(2):87-95
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: HER-2/neu is the most frequently amplified oncogene in breast cancer. Topoisomerase II-alpha is a key enzyme in DNA replication and it is a molecular target for many anti-cancer drugs that are called topo II inhibitors; in addition, it is a new marker of proliferation. Because of the physical proximity of the ER-2/neu and topoisomerase II-alpha genes, co-amplification of the HER-2/neu and topoisomerase II-alpha may be important determinates of the response to chemotherapy for advanced breast cancer patients. METHODS: We studied the correlation of gene amplification of HER-2/neu and topoisomerase II-alpha by chromogenic in situ hybridization (CISH) in 43 infiltrating duct carcinomas of the breast. The over-expression of HER-2/neu protein and the staining index for the proliferation marker of topoisomerase II-alpha were examined immunohistochemically. The correlations between the status of HER-2/neu and topoisomerase II-alpha and the other clinicopathologic variables such as tumor size, lymph node metastasis, TNM stage, histologic grade, nuclear grade, and the estrogen receptor and progesteron receptor were investigated. RESULTS: Of the 43 infiltrating ductal carcinomas, the amplifications of HER-2/neu and topoisomerase II-alpha by CISH were observed in 8 cases (18.6%) and 14 cases (32.6%), respectively. Amplification of HER-2/neu showed the statistically significant correlations with tumor size, histologic grade and the topoisomerase II-alpha staining index. Amplification of topoisomerase II-alpha showed statistically significant correlations with axillary lymph node metastasis, the stage, the nuclear grade and the estrogen receptor status. CONCLUSION: These data suggest that amplification of HER-2/neu oncogene and topoisomerase II-alpha by CISH may be valuable for determining the response to chemotherapy, and detection of HER-2/neu and topoisomerase II-alpha in tumor sections may have prognostic value in human breast cancer.
