Metaplastic carcinoma of the breast shows squamous, sarcomatous or chondromatous differentiation and has a poorer prognosis than usual infiltrating ductal carcinoma. Laminin 5 is a heterotrimer of α3, β3 and χ2 chains and induces aggressive properties in cancer cells including motility, invasion and epithelial to mesechymal transition. Twenty-one cases from 3 institutions revealed 5 squamous, 4 sarcomatous, 6 chondroid and 1 fibromatosis-like metaplastic carcinomas and 5 cases with two metaplastic components. Each of these tumors were stained with antibodies against the laminin 5-specific β3 and χ2 chains, and with antibodies to p63 and cytokeratins 5 and 6 (CK 5/6). Adjacent normal breast showed staining of the myoepithelum by all 4 antibodies. Both of the laminin 5 antibodies stained 20/21 (95.2%) of the tumors, in an identical distribution of the two chains in 90% of the positively staining cases. In contrast, p63 and CK 5/6 each stained 66.7% of the tumors. None of four breast sarcomas, including 1 malignant phyllodes tumor, one angiosarcoma and two undifferentiated sarcomas stained for either of the laminin5 chains or CK5/6, but 1 of 4 (25%) stained for p63. Laminin 5 expression in metaplastic carcinomas is of interest for several reasons. First, this is the only breast carcinoma subtype to demonstrate laminin 5 staining. Second, this data provides additional evidence of the myoepithelial and basal-like phenotype of metaplastic carcinomas. Third, since laminin 5 induces tumor cell invasion and epithelial to mesenchymal transition in vitro, the expression of laminin 5 in metaplastic carcinomas may suggest a mechanism to explain their increased aggressiveness compared with other breast carcinomas. Finally, the results of this study show that compared to other myoepithelial markers, laminin 5 is more sensitive than those previously published, including p63 and CK 5/6. Thus laminin 5 may be helpful for making the diagnosis of metaplastic carcinomas in biopsies. This is important because these highly malignant tumors may require aggressive early treatment including neoadjuvant chemotherapy.

This study was funded by the Avon Foundation.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA