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

Arch Pathol Lab Med. 2004 Oct;128(10):1136-41. doi: 10.5858/2004-128-1136-IEOMMA.

Abstract

Context: 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.

Design: 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.

Conclusion: 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.

MeSH terms

  • Dermatofibrosarcoma / enzymology*
  • Dermatofibrosarcoma / pathology
  • Formaldehyde / metabolism
  • Histiocytoma, Benign Fibrous / enzymology*
  • Histiocytoma, Benign Fibrous / pathology
  • Humans
  • Immunohistochemistry / methods*
  • Matrix Metalloproteinase 1 / biosynthesis
  • Matrix Metalloproteinase 1 / immunology
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / immunology
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / immunology
  • Matrix Metalloproteinases / biosynthesis*
  • Matrix Metalloproteinases / immunology
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / biosynthesis
  • Metalloendopeptidases / immunology
  • Paraffin Embedding / methods
  • Skin Neoplasms / enzymology*
  • Skin Neoplasms / pathology
  • Tissue Fixation / methods

Substances

  • Formaldehyde
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1