Membrane type 1 matrix metalloproteinase (MT1-MMP) has been identified as an activator of the
proenzyme of
matrix metalloproteinase 2 (
MMP-2:
gelatinase A), and has also been shown to play a crucial role in
tumor invasion by activating proMMP2 in both lung and gastric
carcinoma. The
tissue inhibitor of metalloproteinase 2 (TIMP-2) plus the
MT1-MMP complex also plays an important role in the activation of
proMMP-2. In this study, the expressions of
MT1-MMP, MMP-2 and
TIMP-2 were evaluated in 10
enchondromas, 34 conventional
chondrosarcomas, 5
clear-cell chondrosarcomas, 7
mesenchymal chondrosarcomas and 8 dedifferentiated
chondrosarcomas. The expressions were immunohistochemically visualized on
paraffin sections and the levels of expression were assessed semiquantitatively. The extent of staining was assessed by the extent score in order to determine the overall level of expression. The extent scores of
MT1-MMP, MMP-2 and
TIMP-2 in grade 2
chondrosarcoma were significantly higher than those in either
enchondroma or grade 1
chondrosarcoma (P < 0.05). In conventional
chondrosarcoma, significant correlations were found between the extent scores of
MT1-MMP and MMP-2 (P < 0.001),
MT1-MMP and
TIMP-2 (P < 0.01), and MMP-2 and
TIMP-2 (P < 0.01). The undifferentiated small round
tumor cells of
mesenchymal chondrosarcoma showed lower positive rates and extent scores for
MT1-MMP (2/7, 0.7 +/- 0.5) and MMP-2 (3/7, 0.7 +/- 0.4) than for cartilaginous components of
mesenchymal chondrosarcoma [MT1-
MMP (4/7, 1.3 +/- 0.5) and MMP-2 (7/7, 1.9 +/- 0.3)] or conventional
chondrosarcoma. In dedifferentiated
chondrosarcoma, the extent scores of
MT1-MMP, MMP-2 and
TIMP-2 in low-grade cartilaginous components were not significantly different from those in conventional
chondrosarcoma; however, the high-grade anaplastic components showed high extent scores for
MT1-MMP, MMP-2 and
TIMP-2, compared with the low-grade cartilaginous components of dedifferentiated
chondrosarcoma or conventional
chondrosarcoma. According to our results, the expression of
MT1-MMP as well as that of MMP-2 or
TIMP-2 demonstrated a significant correlation with the
tumor grade in human cartilaginous
tumors. Furthermore, the expressions of
MT1-MMP, MMP-2 and
TIMP-2 were also found to play a crucial role in invasion in the high-grade components of dedifferentiated
chondrosarcoma.