Correlation between β-catenin widespread nuclear expression and matrix metalloproteinase-7 overexpression in sporadic desmoid tumors

Hiroshi Matono, Yoshinao Oda, Mari Nakamori, Sadafumi Tamiya, Hidetaka Yamamoto, Ryohei Yokoyama, Tsuyoshi Saito, Yukihide Iwamoto, Masazumi Tsuneyoshi

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21 Citations (Scopus)

Abstract

Desmoid tumors (desmoid-type fibromatoses) are locally aggressive soft tissue tumors associated with the Wnt/β-catenin signaling pathway (APC-β-catenin-Tcf pathway). Matrix metalloproteinase-7, which is one of the target genes of the Wnt/β-catenin signaling pathway, has been reported to play an important role in tumor progression. We examined the immunohistochemical expression of β-catenin and matrix metalloproteinase-7 in 72 samples (63 primary and 9 recurrent samples, 63 patients) of sporadic desmoid tumors without familial adenomatous polyposis, and the genetic alteration of the β-catenin gene in 33 frozen materials (22 primary and 11 recurrent samples, 22 patients). We further examined messenger RNA expression of matrix metalloproteinase 7 by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and compared the results with those of normal skeletal muscles. Immunohistochemically, there was a statistically significant correlation between widespread nuclear expression of β-catenin and overexpression of matrix metalloproteinase-7 (P < .01 in extra-abdominal desmoid, Fisher test). There were 7 missense point mutations in the 22 primary frozen samples (32%). In the β-catenin mutated group, matrix metalloproteinase-7 messenger RNA expression was significantly higher than that of the β-catenin wild-type group (P = .0018, Mann-Whitney U test). Our results suggest that the matrix metalloproteinase-7 gene may be up-regulated by mutated or continuously elevated β-catenin protein and that the matrix metalloproteinase-7 gene may also be targeted in the Wnt/β-catenin signaling pathway in sporadic desmoid tumors.

Original languageEnglish
Pages (from-to)1802-1808
Number of pages7
JournalHuman Pathology
Volume39
Issue number12
DOIs
Publication statusPublished - Dec 1 2008

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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