ErbB2 immune response in breast cancer patients with soluble receptor ectodomain

Investigation of ErbB2 immunity in human breast cancer employing recombinan t expression sources in. immunoblot analysis revealed ErbB2-specific antibo dies of the IgG isotype in sera of 14 of 71 cancer patients and 1 of 31 nor mal donors. Reactivity was confirmed on ErbB2-specific immunoprecipitates. Independent evidence of existing ErbB2 immunity was obtained after in vitro transformation of peripheral blood leukocytes from six positive patients. Furthermore, in vitro immortalization of B-lymphocytes unmasked existent Er bB2 immunity in 1 of 8 patients negative for ErbB2 serum antibodies. Determ ining shed ErbB2 extracellular domain as an indirect measure of tumor burde n in ErbB2-positive malignancy, elevated serum levels were observed in 16 o f 71 breast cancer and 1 of 31 normal donor sera Strikingly, existing ErbB2 immunity correlated significantly with elevated shed ErbB2 ectodomain amon g the patients analyzed. Incidence of both ErbB2 immunity and elevated ErbB 2 extracellular domain increased with a progressed disease stage and was si gnificantly associated with metastatic breast cancer. These observations im plicate soluble ErbB2 amounts in vivo in the development of ErbB2 immunity in breast canter. They further project serum analysis of ErbB2 immunity and soluble ectodomain as potential markers of disease progression in ErbB2-po sitive malignancy.