title: Matrix metalloproteinase-2 expression in stromal  tissues is a consistent prognostic factor in stage II  colon cancer.
abstract: For patients with stage II colon cancer, the usefulness of adjuvant chemotherapy remains controversial. Therefore, it is important to identify high-risk indicators. The biological prognostic factors for recurrence might allow further insight into the optimal treatment strategy for patients with node-negative disease. Matrix metalloproteinase-2 seems to be one of the essential factors for tumor invasion and lymph node metastasis. In this study, we analyzed the expression of cyclooxygenase-2 and matrix metalloproteinase-2 by immunohistochemical staining in 109 patients with stage II colon cancer. A positive correlation was observed between tumor cyclooxygenase-2 and tumor matrix metalloproteinase-2 expression (P = 0.0006) and between tumor cyclooxygenase-2 and stromal matrix metalloproteinase-2 expression (P < 0.0001). Stromal matrix metalloproteinase-2 expression was associated with disease-free survival (P = 0.0095) and was shown to be an independent risk factor for recurrence by multivariate analysis. In addition, we carried out an invasion assay in vitro to investigate whether cyclooxygenase-2 and matrix metalloproteinase-2 affected the tumor-invasive potential of colon cancer cell lines. The invasion assay showed that every cancer cell line acquired invasive potential in coculture with stromal cell lines and the cyclooxygenase-2 inhibitor suppressed this phenomenon by downregulating the matrix metalloproteinase-2 expression of stromal cells. In conclusion, these findings suggest that matrix metalloproteinase-2 expression in stromal cells can be a high-risk indicator for recurrence in patients with stage II colon cancer.
authors.affiliation: Sapporo Medical University, First Department of Surgery, 060-8543 South 1 West 16 Chuo-ku, Sapporo, Japan. inafuku@sapmed.ac.jp
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Inafuku
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Furuhata
authors.forename: Makoto
authors.initials: M
authors.lastname: Tayama
authors.forename: Kenji
authors.initials: K
authors.lastname: Okita
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nishidate
authors.forename: Toru
authors.initials: T
authors.lastname: Mizuguchi
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D002460:Cell Line; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000201:enzymology* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2