Numerous studies have demonstrated a correlation of
matrix metalloproteinase (
MMP) overexpression with the prognosis of various kinds of
cancer. The current study investigated whether the expression of
MMPs is correlated with the prognosis of
osteosarcoma. Expression levels of MMP-2, -9,
MT1-MMP and
TIMP-2 were examined immunohistochemically in samples from 47 patients with
osteosarcoma. Correlation of the positivity of staining with prognosis was analyzed with the Kaplan-Meier method, and statistically analyzed with log-rank test. Co-localization of MMP-2,
MT1-MMP and
TIMP-2 was determined by double staining with fluorescence-conjugated
antibodies. Activities of
gelatinases in representative tissues were examined with
gelatin zymography. MMP-2 was expressed strongly in 60% of cases (28/47), and MMP-9, MT1-
MMP and
TIMP-2 was strongly positive in 61% (29/47), 45% (21/47), and 91% (43/47), respectively. Increased
MT1-MMP expression was associated significantly with poor prognosis in overall survival (P=0.0480). In cases of overexpression for both MMP-2 and
MT1-MMP, there was a tendency for poor prognosis (P=0.0969). In 36 cases who underwent
neoadjuvant chemotherapy, wide resection of the
tumors and post-operative
adjuvant chemotherapy, increased expression of
MT1-MMP resulted in a significant negative prognostic factor for disease-free survival (P=0.0143). Also, co-overexpression of
MT1-MMP and MMP-2 showed a tendency to correlate to the reduced disease-free survival (P=0.0502). Increased
gelatinase activity was observed in tissues of co-overexpression of
MT1-MMP and MMP-2. The results of this study demonstrate the correlation of
MT1-MMP expression and the oncological outcome of
osteosarcoma patients, suggesting the prognostic significance of these
proteins in
osteosarcoma patients.