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 in breast-cancer patients. Our earlier results, now confirmed in a larger cohort 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 expression 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 correlate with erbB-2 expression. However, HLA-A2-positive tumors preferentially showed intratumoral lymphocyte localization, whereas the lesions displaying undetectable HLA-class-I expression showed peritumoral CD3(+) T-cell localization. Taking into account erbB-2 immunoreactivity, we found that the relationship between HLA-A2 expression and intratumoral CD3(+) T-lymphocyte localization 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 breast cancer. Int. J. Cancer (Pred. Oncol.) 84:598-603, 1999.
Nisticò
P
P
Laboratory of Immunology, CRS Regina Elena Cancer Institute, Rome, Italy. nistico@crs.ifo.it
Mottolese
M
M
Cascioli
S
S
Benevolo
M
M
Del Bello
D
D
Di Modugno
F
F
Rubiu
O
O
Gentile
F P
FP
Botti
C
C
Venturo
I
I
Natali
P G
PG
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D005260:Female; D015788:HLA-A1 Antigen / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007157:Immunologic Surveillance / Q000276:immunology*; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D017252:CD3 Complex; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases