Expression of MAGE tumour-associated antigens is inversely correlated withtumour differentiation in invasive ductal breast cancers: an immunohistochemical study

MAGE (Melanoma antigen E) family gene products encompass tumour-associated antigens (TAAs) recognised by human leukocyte antigen (HLA)-restricted spec ific T-cells. Agents inducing DNA demethylation, an event typically detecta ble in cellular de-differentiation processes, were shown to induce the expr ession of MAGE genes. By using a monoclonal antibody specific for MAGE fami ly gene products, we have studied the expression of these TAAs in a group o f 144 patients with invasive ductal breast cancers. Immunohistochemical dat a were correlated with tumour differentiation, lymphatic vessel invasion, o estrogen receptor expression, intratumoural necrosis, lymphocytic infiltrat ion, perineural invasion, tumour microcalcifications and axillary lymph nod e metastases. MAGE immunoreactivity was undetectable in non-neoplastic cell s. In poorly differentiated cancers positive staining was observed in 30/63 cases (47.6%) as compared with 13/51 (25.4%) and 5/30 (16.6%) in moderatel y and well-differentiated tumours, respectively (P <0.05). In addition, MAG E immunoreactivity was significantly correlated with lymphatic vessel invas ion and intratumoural necrosis. Moreover, a significant inverse relationshi p with oestrogen receptor expression was also observed. However, no signifi cant correlation could be established between MAGE immunoreactivity and def ined phenotypic characteristics of tumour infiltrating lymphocytes, includi ng expression of CD3, CD4, CD8, CD20 or granzyme B. Thus, expression of MAG E family gene products in invasive ductal breast cancers appears to be asso ciated with poorly differentiated histological phenotypes. These data suppo rt the concept of specific immunotherapy in highly aggressive forms of brea st neoplasms. Furthermore, they suggest that MAGE immunoreactivity could re present a tumour marker of potential prognostic relevance.