Epithelial-to-mesenchymal transition predicts prognosis of pancreatic cancer

Suguru Yamada, Bryan C Fuchs, Tsutomu Fujii, Yoshie Shimoyama, Hiroyuki Sugimoto, Shuji Nomoto, Shin Takeda, Kenneth K Tanabe, Yasuhiro Kodera, Akimasa Nakao
Surgery 2013, 154 (5): 946-54

BACKGROUND: Pancreatic cancer has a dismal prognosis that is attributed to common local invasiveness and metastasis. Epithelial-to-mesenchymal transition (EMT) plays an important role in cancer invasion and metastasis and is associated with early dissemination. The aim of this study was to evaluate the association between EMT and the prognoses for patients with pancreatic cancer.

METHODS: Immunohistochemistry of E-cadherin and vimentin was performed on surgical specimens from 174 patients who underwent resection of their pancreatic cancers. Tumoral stainings of E-cadherin and vimentin were graded, and EMT statuses were determined by calculating the ratio of vimentin to E-cadherin, whereby patients were categorized into 3 groups: epithelial, intermediate, and mesenchymal. The correlations between EMT statuses and clinicopathologic factors and prognoses were analyzed.

RESULTS: There was a significant correlation between EMT status and CA19-9 levels (P = .020); peritoneal washing cytology (P = .025); portal vein invasion (P = .038); and lymph node metastasis (P = .030). The median survival for patients with epithelial tumors was 40.2 months as compared to 13.7 months for patients with mesenchymal tumors. Multivariate analysis demonstrated that perineural invasion (P = .024); lymph node metastasis (P = .033); and EMT status (P < .0001) were significant prognostic factors. It is interesting that adjuvant chemotherapy (gemcitabine and/or S-1) improved the median survival time from 10.8 to 16.1 months in patients with mesenchymal tumors (P = .002); however, no significant difference was seen in patients with epithelial tumors.

CONCLUSION: EMT status is an important prognostic factor for pancreatic cancer and is associated with portal vein invasion and lymph node metastasis.

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