Human DNA topoisomerase II-alpha: A new marker of cell proliferation in invasive breast cancer
| Autor: | Beverly J. Lynch, Joseph A. Holden, Donald G. Guinee |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Mitotic index Receptor ErbB-2 Mammary gland Breast Neoplasms Biology Pathology and Forensic Medicine Breast cancer Antigens Neoplasm Biomarkers Tumor medicine Carcinoma Humans Neoplasm Invasiveness Doxorubicin Aged Aged 80 and over Cell growth Topoisomerase Middle Aged medicine.disease Immunohistochemistry Molecular biology DNA-Binding Proteins Isoenzymes DNA Topoisomerases Type II Ki-67 Antigen medicine.anatomical_structure biology.protein Female Cell Division medicine.drug |
| Zdroj: | Human Pathology. 28:1180-1188 |
| ISSN: | 0046-8177 |
| DOI: | 10.1016/s0046-8177(97)90256-2 |
| Popis: | DNA topoisomerase II-alpha is the molecular target of doxorubicin, an active drug used in the therapy of breast cancer. From many in vitro studies, it is known that high levels of topo II-alpha expression correlate with drug sensitivity, and low levels of topo II-alpha correlate with drug resistance. In addition, the enzyme is known to be a marker of cell proliferation in normal tissues. Because the number of proliferating cells in a breast cancer has been shown to be prognostically important, and because doxorubicin is used in the treatment of breast cancer, we hypothesized that the measurement of topo II-alpha in breast cancer may not only give drug sensitivity information but also may yield important data on cell proliferation. In this study, formalin-fixed, paraffin-embedded tissue from 30 specimens of invasive breast cancer from 20 patients were immunohistochemically stained for topo II-alpha with a mouse monoclonal antibody. For each case, a topo II-alpha index was determined that represents the number of positive-staining tumor cells divided by the total number of tumor cells counted times 100. A similar index was determined for MIB1, a known cell proliferation marker. Each case was also graded according to the modified Bloom-Richardson criteria and evaluated for c-erbB-2 amplification, hormonal status, S-phase fraction, and mitotic index. The topo II-alpha index correlates better with the MIB1 index than with the S-phase fraction or mitotic index. The topo II-alpha expression in breast cancer ranges from low (topo II-alpha index |
| Databáze: | OpenAIRE |
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