Host immunosurveillance contributes to the control of erbB-2 overexpression in HLA-A2-breast-cancer patients

Overexpression of gp185(erbB-2) has been associated with reduced survival i n breast-cancer patients. Our earlier results, now confirmed in a larger co hort of patients (798), evidenced that the HLA-A2 allele may participate in the modulation of the erbB-2 tumor phenotype in vivo, In the present study , we evaluated other clinico-biopathologic parameters possibly involved in the host immune response against erbB-2, Localization of the CD3(+) T-cell infiltrate was taken into consideration in 705 primary breast tumors, and e xpression of HLA-class-I and HLA-A2 antigens was evaluated in a subgroup of 170 frozen primary tumors of HLA-A2-positive patients, The presence or the absence of HLA-class-I and HLA-A2 antigens in primary tumors did not corre late with erbB-2 expression. However, HLA-A2-positive tumors preferentially showed intratumoral lymphocyte localization, whereas the lesions displayin g undetectable HLA-class-I expression showed peritumoral CD3(+) T-cell loca lization. Taking into account erbB-2 immunoreactivity, we found that the re lationship between HLA-A2 expression and intratumoral CD3(+) T-lymphocyte l ocalization is significant only in the erbB-2 negative subset, whereas the relationship between lack of HLA-class-I expression and peritumoral CD3(+) T-lymphocyte localization is significant only in the erbB-2-positive subset , These data provide novel in vivo evidence of the possible contribution of the host immune system to control of erbB-2 oncogene overexpression in bre ast cancer. Int. J. Cancer (Pred. Oncol.) 84:598-603, 1999. (C) 1999 Wiley- Liss, Inc.