Low Frequency of ErbB-2 Proto-oncogene Overexpression in Human Leukocyte Antigen-A2-Positive Breast Cancer Patients

Extract

Major histocompatibility complex class I molecules act as antigen-presenting molecules to CD8 ⁺ T cells by displaying short peptide fragments derived from intracellular proteins ( 1–3 ). Their role in the recognition and rejection of tumor cells in vivo is not well defined, despite available data demonstrating the existence of immunodominant peptides recognized by cytotoxic T lymphocytes (CTLs) in the context of different human leukocyte antigen (HLA) molecules ( 4–6 ).

The HER-2/ ^neu gene (ErbB-2) encodes a transmembrane glycoprotein (gp185 ^neu ); this glycoprotein is a member of a family of receptors, including epidermal growth factor receptor (EGFR), ErbB-3, and ErbB-4, that have tyrosine kinase activity ( 7–8 ). The overexpression of gp 185 ^neu has been associated with a reduced survival for patients with breast or ovarian cancer ( 9 ). Peptide analysis revealed that ErbB-2 peptides are crucial T-cell epitopes recognized by HLA-A2-restricted tumorspecific CTLs ( 10–12 ). We have been able to stimulate in vitro CD8 ⁺ peripheral blood lymphocytes of breast cancer patients with ErbB-2 peptides that contain HLA-A2.1-binding motifs (Nisticò P, Del Bello D, Mammi C, Cascioli S, Di Modugno F, Natali PG: manuscript in preparation). In the present study, we determine whether a relationship exists in vivo between the HLA-A2 phenotype and ErbB-2 overexpression in the context of different clinicopathologic parameters in primary breast cancer.