Carcinogenesis Advance Access published online on August 27, 2004
Carcinogenesis, doi:10.1093/carcin/bgh270
© 2004 by Oxford University Press
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1 First Department of Internal Medicine, Sapporo Medical University, Sapporo 060-8543, Japan
* To whom correspondence should be addressed. E-mail: h-yama{at}sapmed.ac.jp.
Expression of matrilysin-2, matrix metalloproteinase (MMP)-26, has been implicated in the progression of several types of human cancer. Matrilysin-2 has been reported to be a physiological and pathological activator of pro-MMP-9. The aim of this study was to examine matrilysin-2 expression and determine whether it is correlated with progression of human esophageal squamous cell carcinoma (ESCC). Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemical analysis, zymography, and an in vitro invasion assay were performed. Matrilysin-2 mRNA expression was undetectable or only faintly detected in nontumor tissues but its overexpression was detected in 24 of the 50 ESCC tissues. Matrilysin-2 overexpression was significantly correlated with depth of invasion, lymph node metastasis, and advance in pathological tumor-node-metastasis (TNM) stage. Sections with immunostaining signals in over 10% of carcinoma cells at the invasive front, which were observed in 46 of 100 cases, were judged to be positive for matrilysin-2 expression. Matrilysin-2 expression was significantly correlated with depth of invasion, lymph node and distant metastasis, advance in pathological TNM stage, and recurrence. Expression of matrilysin-2 was significantly correlated with nuclear
Revised July 21, 2004
Accepted August 10, 2004
CANCER BIOLOGY
Association of matrilysin-2 (MMP-26) expression with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma
2 Keiyuhkai Institute of Pathology, Sapporo 030-0027, Japan
3 Department of Surgery, Keiyuhkai Sapporo Hospital, Sapporo 030-0027, Japan
4 Department of Clinical Laboratory Science, Yamaguchi University School of Medicine, Ube 755-8505, Japan
Abstract 
-catenin expression and MMP-9 expression. Patients with matrilysin-2-positive cancer had significantly shorter overall and disease-free survival periods than did those with matrilysin-2-negative cancer. Matrilysin-2 expression retained its significant predictive value for overall and disease-free survival in multivariate analysis. Moreover, patients with concomitant expression of matrilysin-2 and MMP-9 had the worst prognosis. Zymography revealed that matrilysin-2 expression was significantly correlated with the expression of active MMP-9 in ESCC tissues. Matrilysin-2-transfected TE-1 ESCC cells showed active MMP-9 activity and were more invasive in vitro compared with mock-transfected TE-1 cells. The results of this study suggest that matrilysin-2, the expression of which is closely correlated with nuclear -catenin expression and active MMP-9 activity, plays a key role in the progression of ESCC.
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