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


OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Weinrach
David M
DM
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Ill, USA.
Wang
Kim L
KL
Wiley
Elizabeth L
EL
Laskin
William B
WB
D018223:Dermatofibrosarcoma / Q000201:enzymology* / Q000473:pathology; D005557:Formaldehyde / Q000378:metabolism; D018219:Histiocytoma, Benign Fibrous / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000276:immunology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000276:immunology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000276:immunology; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000276:immunology; D016612:Paraffin Embedding / Q000379:methods; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D016707:Tissue Fixation / Q000379:methods
D005557:Formaldehyde; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1