Epithelial-mesenchymal transition (EMT) in resected pancreatic cancer

Abstract

4094 Background: EMT plays an important role in tumor invasion and metastases; its detection may have prognostic significance. We examined expression of EMT related proteins in resected pancreatic cancers and correlated results with clinical outcome. Methods: Clinical data/surgical specimens from 34 consecutive pancreatic cancer patients (pts) who underwent pancreatectomy from 1996–2002 were included. Immunohistochemical staining for vimentin (Vim 3B4), E-cadherin (36B5), MIB1 and cytokeratin (CK-AE1/AE3) was performed on formalin fixed paraffin embedded tissues. Percentages of stained cells (cytoplasmic for vimentin and CK, nuclear for MIB1 and membranous for E-cadherin) were recorded. The results were correlated with clinicopathological parameters and survival. Survival analysis (log-rank test, Cox-proportional hazard model), categorical data analysis (Pearson’s chi-square, logistic regression) and Kendall’s tau were performed at the significance level of 0.05. Results: Clinical data/specimens from 34 pts were included: 13 males, median age 66 (range 38–84); SEER stage 1 (2 pts), 2 (27 pts), 3 (5 pts); histological grade 1 (4), 2 (13), 3 (16), 4 (1). Median survival was 15 months (95% CI: 11–24 months). Sixteen pts had adjuvant chemoradiotherapy, 4 pts had chemotherapy, 1 pt had radiation. IHC Results: vimentin (11.8%), MIB1 (100%), E-cadherin (91%) and CK (100%). There was a significant negative association between vimentin and E-cadherin expression (Kendall’s tau = −0.47, p = 0.0024). Vimentin expression correlated with histological grade (exact chi-square p = 0.0247). No associations were found between these proteins and SEER stage, age, treatment or smoking. Univariate analysis revealed histological grade 50% (p = 0.0039) and MIB1 expression >10% (p = 0.0224) were related to better survival. Multivariate analysis using Cox-proportional hazard model revealed the following significant variables: histological grade (hazard ratio (HR) = 11.8, p = 0.0001), age (HR = 1.1, p = 0.0053), MIB1 (HR = 0.9, p = 0.0003) and adjuvant chemotherapy (HR = 0.2, p = 0.0288). Conclusion: Decreased E-cadherin expression (<50% expression) was associated with poorer survival; E-cadherin expression had an inverse correlation with vimentin. Acknowledgement: Supported by OSI Pharmaceuticals. [Table: see text]