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

• Published in: Human pathology 2008-12, Vol.39 (12), p.1802-1808
• Main Authors: Matono, Hiroshi, MD, Oda, Yoshinao, MD, Nakamori, Mari, MD, Tamiya, Sadafumi, MD, Yamamoto, Hidetaka, MD, Yokoyama, Ryohei, MD, Saito, Tsuyoshi, MD, Iwamoto, Yukihide, MD, Tsuneyoshi, Masazumi, MD
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; beta Catenin - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cell Nucleus - metabolism; Child; Child, Preschool; Desmoid tumors; Female; Fibromatosis, Aggressive - genetics; Fibromatosis, Aggressive - metabolism; Fibromatosis, Aggressive - pathology; Gene Expression Regulation, Neoplastic; Humans; Infant; Male; Matrix Metalloproteinase 7 - genetics; Matrix Metalloproteinase 7 - metabolism; Matrix metalloproteinase-7; Middle Aged; Mutation, Missense; Pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; RNA, Neoplasm - analysis; Soft Tissue Neoplasms - genetics; Soft Tissue Neoplasms - metabolism; Soft Tissue Neoplasms - pathology; Wnt signaling; Young Adult; β-catenin
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2008.05.005

Summary 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.