Expression and quantitative analysis of matrix metalloproteinase-2 and -9 in human gliomas.
The matrix metalloproteinase (MMP) family members catalyze extracellular proteolysis. Recent reports have suggested that expression of MMP-2 and -9 might play a critical role in neoplastic tissue invasion or metastasis. In this study, the relationship between the expression of MMP-2 and -9 and the histological features of tissues from 21 cases of human glioma were investigated. MMP-2 and -9 proteins were detected by immnohistochemical studies. Amplification of MMP-2 and -9 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) assay. MMP-2 and -9 mRNA was measured quantitatively by the real-time RT-PCR method. Immunohistochemically, 38% of the cases were positive for MMP-2. Amplification of MMP-2 mRNA by RT-PCR was detected in 62% of the cases. There was no significant relationship between the expression of MMP-2 protein or mRNA and the biological nature of the tumors, including aggressiveness and histologic classification. The quantity of MMP-2 mRNA was 0.035 +/- 0.113 (MMP-2/GAPDH %), which was significantly elevated in cases of neoplastic dissemination or recurrence (P < 0.05). Tumor cells were immunohistochemically positive for MMP-9 in 81% of the samples. A positive reaction was found not only in neoplastic cells but also in endothelial cells, suggesting that the expression of MMP-9 protein might be associated with tumoral angiogenesis. The expression of mRNA in MMP-9 was detected in 91% of the cases, suggesting a close relationship between expression of MMP-9 and malignancy. The quantity of MMP-9 was 0.097 +/- 0.113 (MMP-9/GAPDH %) in all samples, which was significantly elevated in cases of glioblastoma (P < 0.05). The average Ki-67 labeling index was 8.14 +/- 5.26 in samples from G2 glioma, 19.92 +/- 11.29 in samples from G3 glioma, and 23.52 +/- 10.14 in samples from glioblastoma. All of the cases with elevated indices had recurrence or dissemination. The results of our study suggest that quantity analyses of MMP-2 and -9 mRNA and Ki-67 labeling index should be useful for discerning tumoral behaviors such as invasion, dissemination, and recurrence.
Komatsu
Kyoko
K
Pathology Laboratory, Nihon University Itabashi Hospital, 30-1 Ohyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. kkoma@med.nihon-u.ac.jp
Nakanishi
Yoko
Y
Nemoto
Norimichi
N
Hori
Tomokatsu
T
Sawada
Tatsuo
T
Kobayashi
Makio
M
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9