Increased expression of membrane-type matrix metalloproteinase-1 is correlated with poor prognosis in patients with osteosarcoma.
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.
Uchibori
Mitsutoshi
M
Department of Orthopaedic Surgery, Aichi Cancer Center Aichi Hospital, Kake-machi, Okazaki City, Aichi 444-0011, Japan. uchibori@pop02.odn.ne.jp
Nishida
Yoshihiro
Y
Nagasaka
Tetsuro
T
Yamada
Yoshihisa
Y
Nakanishi
Keisuke
K
Ishiguro
Naoki
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology*; D002648:Child; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000502:physiology; D053504:Matrix Metalloproteinases, Membrane-Associated; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9