Expression of Topoisomerase II-alpha and c-erbB-2 in Breast Cancer

Chung, Tae Sung; Kim, Bum Gyu; Cha, Seong Jae; Park, Sung Il; Lim, Hyun Mook; Park, Sung Jun; Lee, Tae Jin

Abstract

PURPOSE: Topoisomerase II-alpha is a key enzyme in DNA replication and a molecular target for many anti-cancer drugs. The C-erbB-2 oncogene (HER-2/neu) is the most frequently amplified oncogene in breast cancer. Because of the physical proximity of c-erbB-2 and topoisomerase II-alpha, co-amplification of the c-erbB-2 and topoisomerase II-alpha may occur. To investigate the clinical significance of the topoisomerase II-alpha and c-erbB-2, the correlation between topoisomerase II-alpha and c-erbB-2 was examined by immunohistochemical staining in 43 invasive ductal breast carcinomas and its relationship with other prognostic factors.
METHODS
Topoisomerase II-alpha and c-erbB-2 expression was studied immunohistochemically using sections of formalin fixed, paraffin-embedded tumor specimens from 43 invasive ductal breast carcinomas. The correlation between topoisomerase II-alpha and c-erbB-2 expression, and its relationship with the clinicopathological factors such as the tumor size, lymph node metastasis, TNM stage, histological grade, nuclear grade, estrogen receptors and progesteron receptors was investigated.
RESULTS
C-erbB-2 was expressed in 9 (20.9%) out of the 43 infiltrating ductal carcinoma cases. Among the prognostic factors, the tumor size, lymph node metastasis, tumor stage, nuclear grade, status of progesteron receptors and estrogen receptors did not significantly correlated with c-erbB-2 expression. The tumor size, lymph node metastasis, tumor stage, histological grade, and the absence of estrogen receptors displayed a significant relationship with the increase in the topoisomerase-alpha index. However, the topoisomerase II-alpha index did not correlate with the nuclear grade and the status of progesterone receptors. The topoisomerase II-alpha index was slightly higher in the c-erbB-2 positive expression cases compared to c-erbB-2 negative expression cases but this increase was not significant (P=0.503).
CONCLUSION
These results suggest that topoisomerase II-alpha may play some role as a prognostic factor, but further investigation is needed.