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KMID : 0371320070730020087
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Journal of the Korean Surgical Society
2007 Volume.73 No. 2 p.87 ~ p.95
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Amplification of the HER-2/neu Oncogene and Topoisomerase II-? by Chromogenic in Situ Hybridization in Breast Cancer
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Kim Ho-Sung
Kim Beom-Gyu
Cha Sung-Jae
Lee Tae-Jin
Park Sung-Jun
Lim Hyun-Muk
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Abstract
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Purpose: HER-2/neu is the most frequently amplified oncogene in breast cancer. Topoisomerase II-? 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-? genes, co-amplification of the HER-2/neu and topoisomerase II-? 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-? 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-? were examined immunohistochemically. The correlations between the status of HER-2/neu and topoisomerase II-? 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-? 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-? staining index. Amplification of topoisomerase II-? 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-? by CISH may be valuable for determining the response to chemotherapy, and detection of HER-2/neu and topoisomerase II-? in tumor sections may have prognostic value in human breast cancer. (J Korean Surg Soc 2007;73:87-95)
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KEYWORD
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HER-2/neu, Topoisomerase II-?, CISH, Breast cancer
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