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Immunohistochemical expression of matrix metalloproteinases 1, 2, 9, and 14 in dermatofibrosarcoma protuberans and common fibrous histiocytoma (dermatofibroma).

Weinrach DM,Wang KL,Wiley EL,Laskin WB

Abstract

Common fibrous histiocytoma (cFH) or dermatofibroma and dermatofibrosarcoma protuberans (DFSP) are 2 spindle cell mesenchymal tumors that are distinguished in part by their microscopic growth patterns and clinically by the greater propensity for DFSP to recur. Matrix metalloproteinases (MMPs) potentially play a role in modulating the growth patterns of cFH and DFSP by remodeling the extracellular matrix.
To evaluate the immunohistochemical (IHC) expression of MMP-1, MMP-2, MMP-9, and MMP-14 in DFSP and cFH, because (1) MMP-1, MMP-2, MMP-9, and MMP-14 are synthesized by dermal fibroblasts, the major constituent of DFSP and cFH; and (2) platelet-derived growth factor B, which is overexpressed in most examples of DFSP because of t(17;22), activates ets-1, a transcription factor that regulates molecules associated with tumor invasion and metastasis, including MMP-1, MMP-3, and MMP-9.
Immunohistochemical studies were performed on archived, formalin-fixed, paraffin-embedded tissue of DFSP (n = 48) and cFH (n = 47).Results.-Significant IHC expression (>10% of tumor cells) in cFH included MMP-14 (27 [59%] of 46 tumors positive), MMP-2 (21 [47%] of 45 tumors positive), MMP-9 (9 [20%] of 45 tumors positive), and MMP-1 (6 [13%] of 46 tumors positive). No DFSPs showed significant IHC expression of any of the MMPs evaluated. However, anti- MMP-2 highlighted a rich microvascular element within deep tumor tissue present in 81% of DFSPs with a prominent subcutaneous component.
Our IHC results indicate that MMP-1 and MMP-9 are not up-regulated in DFSP. Convincing expression of MMP-14 in cFH suggests that this MMP may affect the growth pattern of the lesion, perhaps by activating MMP-2 expression in tumor cells. In DFSP, MMP-2 may play a role in tumor angiogenesis.

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