Matrix metalloproteinase-9 activity is associated with poor prognosis in T3-T4 node-negative colorectal cancer.
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a novel membrane-anchored matrix metalloproteinase (MMP) inhibitor. RECK, MMP-2, and MMP-9 are believed to play crucial roles in tumor progression. This study was designed to examine the prognostic value of RECK, MMP-2, and MMP-9 in conjunction with other clinicopathologic factors in patients of T3-T4 node-negative colorectal cancer. RECK and MMP expression was observed using immunohistochemical analysis of the primary tumor from 89 patients with curatively resected T3-4 N0 colorectal cancer retrospectively. High RECK expression was observed in 51 cases, whereas expression was low in the other 38 cases. MMP-2 and MMP-9 expression was positive in cancer cells in 24 and 33 cases, respectively. RECK and MMP-2 expression was not significantly associated with any clinicopathologic factors. However, expression of MMP-9 was correlated with tumor location. A statistically significant inverse correlation was found between RECK and MMP-2 expression, and a statistically significant correlation was found between MMP-2 and MMP-9 expression. However, no association between RECK and MMP-9 expression was observed. Univariate analysis demonstrated that rectal tumor location, preoperative carcinoembryonic antigen more than 5 ng/mL, positive lymphatic invasion, less than 12 dissected lymph nodes, and positive MMP-9 expression were poor prognostic factors of disease-free survival. A multivariate analysis confirmed that enhanced MMP-9 expression was an independent and significant factor for prediction of a poor prognosis. In addition, positive lymphatic invasion and less than 12 dissected lymph nodes were significant negative prognostic factors. In conclusion, MMP-9 status represents a novel prognostic factor in evaluation of T3-T4 node-negative colorectal cancer.
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea.
Yong Beom
YB
Cho
Woo Yong
WY
Lee
Sang Yong
SY
Song
Hee Jung
HJ
Shin
Seong Hyeon
SH
Yun
Ho-Kyung
HK
Chun
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C115460:RECK protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9