Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma

We examined the expression level of several genes that regulate distinct st eps of metastasis in formalin-fixed, paraffin-embedded, archival specimens of primary human pancreatic carcinomas from patients undergoing curative su rgery, The expression of epidermal growth factor receptor, E-cadherin, type IV collagenase [matrix metalloproteinase (MMP) 2 and MMP-9), basic fibrobl ast growth Factor, vascular endothelial growth factor/vascular permeability factor, and interleukin 8 was examined by a colorimetric in situ mRNA hybr idization technique. Down-regulation of E-cadherin and up-regulation of typ e TV collagenase (MMP-9 and MMP-2) at the periphery of the neoplasms (P = 0 .0167, 0.0102, and 0.0349, respectively) had significant prognostic value. The ratio of type TV collagenase expression (mean of the expression of MMP- 2 and MMP-9) to E-cadherin expression (MMP:E-cadherin ratio) at the periphe ry of the tumors was significantly higher in patients with recurrent diseas e (4.7 +/- 2.1) than in patients who were disease free (2.3 +/- 1.7; P = 0. 0008), Death from pancreatic cancer was significantly associated with a hig h MMP:E-cadherin ratio (>3.0) by overall survival analysis (P < 0.0002), wh ereas a low MMP:E-cadherin ratio (<3.0) was found in seven of eight patient s alive 28-64 months after surgery. Multivariate analysis of overall surviv al showed that the MMP:E-cadherin ratio was a significant independent progn ostic factor, whereas stage, nodal metastasis, and histological type were n ot. These data show that multiparametric analysis for several metastasis-re lated genes may allow physicians to assess the metastatic potential and hen ce predict the clinical outcome of individual patients with resectable panc reatic carcinoma.