The high molecular weight melanoma-associated antigen, defined by murine monoclonal antibody (IgG1) 225.28S is largely expressed by melanoma cells and weakly expressed by other human tumors originating from neural crest. In this study, we analyzed the immunohistochemical reactivity of MoAb 225.28S in human breast cancer biopsies. A total of 92 breast cancer biopsies (66 infiltrating lobular and 26 infiltrating ductal carcinomas) were initially tested along with 26 melanomas (positive controls), 23 gastric/colonic adenocarcinomas and 13 neuroendocrine tumors. Forty-four out of 66 lobular breast carcinomas showed positive immunostaining with 225.28S MoAb as well as only 6 out of 26 infiltrating ductal histotype and 12 out of 26 melanomas. Conversely, gastric and colonic adenocarcinomas and neuroendocrine tumors were completely negative. The pattern of positivity in breast carcinomas was associated with malignant cells, rather than with the stroma or histiocytes infiltrating the lesions. Nonspecific cross-reactivity of 225.28S with breast carcinomas was excluded using a similar murine antithyreoglobulin MoAb, which gave negative staining in all biopsies. These results indicated that HMW-MAA or a similar sequence recognized by 225.28S MoAb is often expressed by lobular breast carcinomas but rarely by ductal adenocarcinomas. This seems to suggest that lobular breast carcinoma has common "ancestor" antigens with melanoma.

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