title: Elevations of DNA topoisomerase I in invasive carcinoma of the breast.
abstract: DNA topoisomerase I (topo I) is the molecular target of the camptothecin group of anticancer drugs. Laboratory experiments indicate that breast cancer cell lines are sensitive to these agents and recent clinical trials have suggested that some breast cancer patients may respond to drugs targeting topo I. Since it is known that cells responding to topo I-targeted drugs have elevated levels of topo I, these results suggest that some breast cancers may have elevated expression of the enzyme. To test this we used a new topo I monoclonal antibody to immunostain 22 primary breast cancers and 5 lymph nodes with metastatic disease. Tissue was fixed in formalin and paraffin embedded. Expression of topo I was subjectively determined by noting the intensity of the immunostain. We found increased expression of topo I in 41% (9/22) of the primary tumors. We conclude that immunohistochemical staining of breast cancers for topo I can be easily performed and may help in defining the molecular parameters of those neoplasms sensitive to drugs targeting the enzyme.
authors.affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Lynch
authors.forename: I B
authors.initials: IB
authors.lastname: Bronstein
authors.forename: J A
authors.initials: JA
authors.lastname: Holden
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D002166:Camptothecin / Q000494:pharmacology / Q000627:therapeutic use; D004264:DNA Topoisomerases, Type I / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D013194:Staining and Labeling
chemical_list: D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin