Abstract 458: Implication of epithelial to mesenchymal transition (EMT) in pancreatic cancer prognosis

Abstract

Abstract [Background] In recent years, epithelial-to-mesenchymal transition (EMT) has been shown to play an important role during cancer invasion and metastasis, and is now being actively studied in various cancers. Moreover, EMT is thought to be involved in resistance to chemotherapy and this elucidation could contribute to improved therapeutic effect. A thorough examination of EMT in pancreatic cancer, especially using resected surgical specimens, has not been conducted to date. [Methods] Between April 2004 and March 2010, 174 patients who underwent the resection of their pancreatic cancers were used for this study. Immunohistochemistry of E-cadherin and Vimentin were performed on their resected specimens, and the results of the staining were graded as follows; grade 1: negative, grade 2: positive, grade 3: strong positive. V/E ratio (Vimentin grade/E-cadherin grade) was determined and the patients were categorized into three group as follows: Epithelial(E)1. The correlation between EMT status and clinicopathological factors were analyzed. [Results] 1. Of the 174 cases, EMT status was determined as 37 Epithelial, 48 Borderline and 89 Mesenchymal. We found a significant correlation between EMT status and washing cytology (P = 0.025), tumor size (P = 0.014), portal vein invasion (P = 0.038) and lymphatic invasion (P = 0.047). 2. The median survival was 40.2 months in E, 63.1 months in B, and 13.7 months in M, respectively. There was a significant difference between M and E, and M and B (P < .0001). 3. According to univariate analysis, tumor location (head), CA19-9 level, tumor size (≥ 2cm), anterior tumor invasion, bile duct invasion, duodenal invasion, portal vein invasion, lymphatic or vascular invasion, positive perineural invasion, lymph node metastasis and EMT status (B · M / E) were found to be significant prognostic factors. Multivariate analysis showed perineural invasion (P = 0.024), lymph node metastasis (P = 0.033) and EMT status (P <0.0001) were significant prognostic factors. 4. Adjuvant chemotherapy (gemcitabine or S-1) improved the median survival from 19.9 to 63.1 months in group B, from 10.8 to 16.1 months in group M (P = 0.034, P = 0.002, respectively), however, no significant difference was seen in group E. [Discussion] EMT status was found to be one of the most important prognostic factors in pancreatic cancer and suspected to be associated with cancer invasion and metastasis. Further studies are needed to validate these results, but chemotherapy strategies targeted to epithelial and mesenchymal tumors might improve the outcomes of this disease by increasing the effect of chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 458. doi:1538-7445.AM2012-458