Membrane-type-1 matrix metalloproteinase, matrix metalloproteinase 2, and tissue inhibitor of matrix proteinase 2 in prostate cancer: identification of patients with poor prognosis by immunohistochemistry.
Overexpression of the matrix metalloproteinase (MMP) 2 is associated with poor prognosis in many tumor types. Membrane-type-1 MMP (MMP14) activates MMP2 using pro-MMP2 specific inhibitor, tissue inhibitor of matrix proteinase 2 (TIMP2), as a receptor. We evaluated, by immunohistochemistry on 189 T3N0-2M0 prostate cancer (Pca) cases, the influence of MMP2, MMP14, and TIMP2 expression, individually and in association, on Pca disease-free survival (DFS). We evaluated marker expression separately in cancer, stromal, and benign epithelial (BE) cells according to a percentage scale (0%, <10%, 10%-50%, and >50%). Median follow-up was 4.61 years. In BE cells, there was an inverse relationship between initial prostate-specific antigen serum level and T3 stage with MMP14 expression (P = .003) and between pN stage and TIMP2 expression (P = .04). The most significant results with survival were obtained by dichotomizing the cases between those with less than 10% and at least 10% of cells expressing the marker, the latter category representing overexpression. TIMP2 overexpression in stromal cells was associated with a longer DFS with a hazard ratio of 0.573 (P = .02) for time to recurrence. MMP2 overexpression by BE cells correlated with a shorter DFS using a multivariate trend test (hazard ratio = 1.46, P = .02). Stromal cells expressing less than 10% TIMP2 and MMP2 overexpression was the only combination that was significantly associated with a shorter DFS (log-rank test, P = .0001). This study suggests that MMP14 is involved mostly in Pca implantation and that MMP2 and TIMP2 expression by reactive stromal cells might be used as predictors of DFS in T3N0-2M0 Pca.
Trudel
Dominique
D
Department of Pathology, Centre Hospitalier Universitaire de Québec (CHUQ) and Université Laval, Québec, Canada G1K 7P4.
Fradet
Yves
Y
Meyer
François
F
Harel
François
F
Têtu
Bernard
B
D000328:Adult; D000368:Aged; D002170:Canada / Q000453:epidemiology; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14