Open AccessMatrix metalloproteinase‐2 expression in stromal tissues is a consistent prognostic factor in stage II colon cancer
Author(s) -
Inafuku Yoshiko,
Furuhata Tomohisa,
Tayama Makoto,
Okita Kenji,
Nishidate Toshihiko,
Mizuguchi Toru,
Kimura Yasutoshi,
Hirata Koichi
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01116.x
Subject(s) - stromal cell , colorectal cancer , medicine , metastasis , matrix metalloproteinase , immunohistochemistry , cyclooxygenase , cancer research , cancer , pathology , oncology , biology , enzyme , biochemistry
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. ( Cancer Sci 2009; 100: 852–858)