EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA, AMPHIREGULIN AND CRIPTO-1 IN HUMAN BREAST CARCINOMAS

The expression of three epidermal growth factor (EGF)-related peptides , transforming growth factor alpha (TGF-alpha), amphiregulin (AR) and cripto-1 (CR-1), was examined by immunocytochemistry (ICC) in 68 prima ry infiltrating ductal (IDCs) and infiltrating lobular breast carcinom as (ILCs), and in 23 adjacent non-involved human mammary tissue sample s. Within the 68 IDC and ILC specimens, 54 (79%) expressed immunoreact ive TGF-alpha, 52 (77%) expressed AR and 56 (82%) expressed CR-1. Cyto plasmic staining was observed with all of the antibodies, and this sta ining could be eliminated by preabsorption of the antibodies with the appropriate peptide immunogen. Cytoplasmic staining with all of the an tibodies was confined to the carcinoma cells, since no specific immuno reactivity could be detected in the surrounding stromal or endothelial cells. In addition to cytoplasmic reactivity, the AR antibody also ex hibited nuclear staining in a number of the carcinoma specimens. No si gnificant correlations were found between the percentage of carcinoma cells that were positive for TGF-alpha, AR or CR-1 and oestrogen recep tor status, axillary lymph node involvement, histological grade, tumou r size, proliferative index, loss of heterozygosity on chromosome 17p or overall patient survival. However, a highly significant inverse cor relation was observed between the average percentage of carcinoma cell s that expressed AR in individual tumours and the presence of a point- mutated p53 gene. Likewise, a significantly higher percentage of tumou r cells in the ILC group expressed AR as compared with the average per centage of tumour cells that expressed AR in the IDC group. Of the 23 adjacent, non-involved breast tissue samples, CR-1 could be detected b y ICC in only three (13%), while TGF-alpha was found in six (26%) and AR in ten (43%) of the non-involved breast tissues. These data demonst rate that breast carcinomas express multiple EGF-related peptides and show that the differential expression of CR-1 in malignant breast epit helial cells may serve as a potential tumour marker for breast cancer.