Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Topoisomerase II is a key target for several anti-cancer drugs used for breast cancer therapy, including doxorubicin, epirubicin and mitoxantrone. Two isoforms of topoisomerase II (alpha and beta) have been described in human cells which differ in their subcellular localisation, biochemical properties and susceptibility to inhibition by anti-cancer drugs. The relative level of expression of the alpha and beta isoforms may contribute to the degree of tumour responsiveness to different chemotherapeutic agents. To assess the relationship between expression of topoisomerase II isoforms and established prognostic factors and pathological variables, 56 primary breast tumour samples were studied. The expression of the two topoisomerase II genes was apparently not co-ordinately regulated in these tissue samples. There was no relationship between any of the commonly used pathological variables [tumour size, lymph node status, S-phase fraction (SPF)] and the level of expression of topoisomerase II beta mRNA. However, high topoisomerase II alpha gene expression was significantly associated with a high SPF (sign-rank test; P = 0.01). Moreover, the ratio of mRNA levels for topoisomerase II alpha and beta showed a stronger relationship to SPF (median raito 0.62 for tumours with SPF < 10, and 1.64 for SPF > 10; P = 0.0021, sign-rank test). As expected from previous studies, an SPF > 10 was associated with poor overall survival (P = 0.01). Immunohistochemical analysis revealed that topoisomerase II beta was widely distributed ( > 90% positive tumour cells), but that topoisomerase II alpha expression was less widely expressed, with a pattern of expression similar to that of the proliferation-dependent antigen recognised by Ki67. Because topoisomerase II gene expression showed a log-normal distribution, log-transformed data were used in multivariate analysis of relapse-free survival. This showed that lymph node status and topoisomerase II beta mRNA expression were the only significant survival factors (P = 0.001 and 0.05, respectively, with relative risks of 1.3 and 1.8). These results indicate that topoisomerase II alpha, but not beta, expression is dependent upon cellular proliferation status, but that the more widely expressed topoisomerase II beta protein may play a significant role as a target for anti-tumour therapy.

Original publication

DOI

10.1038/bjc.1996.286

Type

Journal article

Journal

Br J Cancer

Publication Date

06/1996

Volume

73

Pages

1518 - 1524

Keywords

Antigens, Neoplasm, Breast Neoplasms, DNA Topoisomerases, Type II, DNA-Binding Proteins, Female, Gene Expression, Humans, Isoenzymes, Ploidies, Prognosis, RNA, Messenger, S Phase