Expression of Cartilage-Specific Markers in Matrix-Producing Carcinoma of the Breast
A Contreras, T Krausz, A Montag, M Tretiakova, R Wilcox, K Gwin. The University of Chicago Medical Center, Chicago, IL
Background: Matrix-producing carcinoma (MPC) is a rare variant of metaplastic breast carcinoma with mixed epithelial and myxochondroid mesenchymal elements. Previous studies indicated that MPC are of epithelial origin and are associated with a myoepithelial-like differentiation. Little is known about the precise matrix composition or if a true chondrogenic transition occurs. The differentiation of mesenchymal cells into chondrocytes involves a multistep pathway and can be traced by evaluating marker genes of chondrocytic development. The transcription factor SOX9 is expressed early in mesenchymal condensation and has, with the chondroitin sulfate proteoglycan versican, an essential function in the subsequent differentiation of prechondrogenic precursor cells into chondrocytes. Differentiated chondrocytes express cartilage-specific markers such as the chondroitin sulfate proteoglycan aggrecan.
Design: Archival paraffin embedded material of 11 MPC as defined by the 2003 WHO classification and 2 axillary lymph node metastasis, one with a cartilaginous matrix component and one without, were examined by IHC for the expression and localization of SOX9, versican, aggrecan, p63 and S100.
Results: Tumor cells within the matrix revealed moderate to strong nuclear staining for p63 (13/13) and nuclear and cytoplasmic staining for S100 (13/13). Strong SOX9 nuclear expression was observed in the metaplastic carcinoma cells (11/11), and moderate SOX9 expression in the adjacent conventional carcinoma and in both lymph node metastasis. Strong staining for versican was observed in a cytoplasmatic pattern in the metaplastic tumor cells as well as the adjacent invasive conventional carcinoma. All 11 cases showed variable degrees of immunoreactivity for aggrecan. None of the cartilage biomarkers were expressed in normal mammary tissue.
Conclusions: MPC display cartilaginous differentiation and express cartilage specific matrix molecules. Our findings support that breast carcinoma cells of initially epithelial origin transdifferentiate into chondrocyte-like cells following the pathway of chondrocytic development. Thus, the results of this suggest that cartilage formation in MPC is a result of (myo)epithelial to mesenchymal transition.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 20, Tuesday Afternoon