Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma

Yorihisa Imanishi, Masato Fujii, Yutaka Tokumaru, Toshiki Tomita, Minoru Kanke, Jin Kanzaki, Kaori Kameyama, Yoshihide Otani, Hiroshi Sato

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Three different membrane-type matrix metalloproteinases (MT-MMPs) activate in vitro the latent form of matrix metalloproteinase-2 (MMP-2), which is one of the key proteinases in invasion and metastasis of various cancers. We examined the mRNA expression of MT1, 2, and 3-MMPs and MMP-2 in cell lines of head and neck squamous cell carcinoma (HNSCC) and quantitated the relative expression levels in human HNSCC tissues by Northern blotting. The tissue localization of MT1-MMP and MMP-2 was determined by immunohistochemistry and in situ hybridization. Their implications in clinicopathologic factors were statistically evaluated. All cell lines examined consistently expressed MT1-MMP and MMP-2, but not MT2, 3-MMP. In the clinical specimens, there was a significant correlation in coexpression of messenger of RNA (P= .0005) and colocalization by immunohistochemistry (P < .0001) for MT1-MMP and MMP-2. Relative mRNA expression levels of MT1-MMP and MMP-2 in the carcinoma tissues were significantly higher than those of the control tissues (P = .0045 and P = .0122, respectively). Both mRNA expression level and immunopositivity of MT1-MMP significantly correlated with lymph node metastasis (P = .0081 and P = .0193, respectively), which was confirmed by multivariate logistic regression analysis. Immunoreaction of MT1-MMP and its mRNA expression were observed in both carcinoma cells and stromal cells. The localization of MMP-2 closely corresponded to that of MT1-MMP. These observations suggest that MT1-MMP possesses a role as a determinant of lymph node metastasis in HNSCC, and that concurrent expression of MT1-MMP and MMP-2 are involved in progression of HNSCC. Copyright (C) 2000 by W.B. Saunders Company.

Original languageEnglish
Pages (from-to)895-904
Number of pages10
JournalHuman Pathology
Volume31
Issue number8
DOIs
Publication statusPublished - 2000 Jan 1

Keywords

  • HNSCC
  • Lymph node metastasis
  • MMP-2
  • MT1-MMP
  • Multivariate logistic regression analysis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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