HIGH-FREQUENCY OF ALTERED HLA CLASS-I PHENOTYPES IN INVASIVE BREAST CARCINOMAS

We studied 105 tumor samples obtained from patients diagnosed as havin g breast carcinomas for HLA class I and II (DR) antigen expression, us ing a panel of mAbs defining HLA-monomorphic, locus-specific and allel e-specific determinants. Peripheral blood lymphocytes from patients we re also typed for HLA alleles. The results indicated total HLA class I losses in 55 patients (52.3%), HLA-A locus losses in four patients (3 .8%), HLA-B locus losses in eight patients (7.6%), and A, B, locus los ses in 10 patients (9.5%). The remaining 28 patients whose tissues rea cted positively with monomorphic- and locus-specific mAbs were tested for HLA allelic losses using several anti-HLA mAbs defining A2, A3, A9 , B8, B12, etc. Of these 25 patients, 16 (57%) showed one or more loss es of HLA reactivity. These results indicated that in 88.5% of patient s we detected a particular HLA-altered tumor phenotype. The downregula tion of HLA class I antigens in breast carcinomas may thus be more fre quent than previously reported, and patients without HLA class I downr egulation may be the exception rather than the rule. It cannot be rule d out that HLA alterations are present in some of the 12 patients with an apparently normal HLA phenotype, as some HLA alleles could not be studied because of the lack of appropriate mAbs. These HLA alterations could represent an important step associated with tumor invasion, con ferring to the tumor cells the ability to escape from T-lymphocyte rec ognition.