Gelatinase B expression as a prognostic factor in patients with stage II/III rectal carcinoma treated by postoperative adjuvant therapy.

ABSTRACT

OBJECTIVE: The matrix-metalloproteinases (MMPs) are thought to be critically involved in tumor invasion and metastasis. This retrospective study was aimed both to examine the gelatinase expression status in patients with rectal cancer and to investigate their prognostic value on survival. METHODS: Sixty patients who underwent postoperative adjuvant chemoradiotherapy for Stage II and III rectal carcinoma were included. Expressions of MMP-2, MMP-9, and tissue inhibitors of MMP (TIMP-1 and TIMP-2) were analyzed by immunohistochemistry in paraffin-embedded primary rectal cancers and graded for the intensity and the percentage of cells stained. The relation between the expression of the markers studied and clinicopathologic features were evaluated for the primary study endpoint. The data were also analyzed using a multivariate Cox proportional hazards model for prognosis as a secondary endpoint. RESULTS: Positive MMP-9 expression was observed in 70% of the tumors. The ratio of tumors with positive MMP-9 expression was increased according to N stage (P = 0.005), AJCC stage (P = 0.005), and tumor differentiation (P = 0.017). Overall survival was reduced in poorly differentiated tumors and tumors with positive MMP-9 expression (P = 0.002). Disease-free survival was lower in patients with positive MMP-9 expression (P = 0.007). Multivariate analysis indicated that positive MMP-9 expression was an independent predictor of reduced overall survival (P = 0.0103) and reduced disease-free survival (P = 0.0360). The other markers studied were associated with neither any clinicopathologic feature nor any survival parameter. CONCLUSION: MMP-9 expression was observed in the tumors of patients with Stage II and III rectal carcinoma in comparable values and was characterized by poor overall survival and disease-free survival.