title: Level of HER-2/neu protein expression in breast cancer may affect the development of endogenous HER-2/neu-specific immunity.
abstract: We questioned whether the incidence or magnitude of the humoral or cellular immune response to the self-tumor antigen HER-2/neu is influenced by the level of HER-2/neu protein overexpression as defined by immunohistochemical staining of tumors in breast cancer patients. We obtained peripheral blood from 104 women with stage II, III, and IV pathologically confirmed HER-2/neu-overexpressing breast cancer. Patients were categorized with +1 (n = 14), +2 (n = 20), or +3 (n = 70) HER-2/neu overexpression by institutional pathologic report. Circulating antibodies to HER-2/neu were evaluated using ELISA. T-cell responses to HER-2/neu were measured using an antigen-specific tritiated thymidine incorporation assay. Eighty-two percent of subjects with HER-2/neu antibodies were +3 overexpressors compared with 18% +2 overexpressors and 0% +1 overexpressors, a highly significant difference (P < 0.001), and there were significant differences in the magnitude of the HER-2/neu-specific antibodies between groups with varying HER-2/neu protein expression (P = 0.022). In addition, 65% of subjects with HER-2/neu-specific T cells were +3 overexpressors compared with 16% +2 overexpressors and 19% +1 overexpressors (P = 0.001). Data presented here indicate that endogenous HER-2/neu-specific humoral and T-cell immunity is greater in patients with +3 protein overexpression in their tumors than in patients with lower levels of HER-2/neu expression. Overexpression of a self-tumor-associated protein is a potential mechanism by which immunogenicity is enhanced and may aid in the identification of biologically relevant proteins to target for immune-based molecular cancer therapies.
authors.affiliation: Tumor Vaccine Group, University of Washington, Seattle, WA 98109-8050, USA. vgoodell@u.washington.edu
authors.forename: Vivian
authors.initials: V
authors.lastname: Goodell
authors.forename: James
authors.initials: J
authors.lastname: Waisman
authors.forename: Lupe G
authors.initials: LG
authors.lastname: Salazar
authors.forename: Corazon
authors.initials: C
authors.lastname: de la Rosa
authors.forename: John
authors.initials: J
authors.lastname: Link
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Coveler
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Childs
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Fintak
authors.forename: Doreen M
authors.initials: DM
authors.lastname: Higgins
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
mesh_terms: D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000912:Antibodies, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases