title: Epithelial-mesenchymal transition (EMT) and activated extracellular signal-regulated kinase (p-Erk) in surgically resected pancreatic cancer.
abstract: BACKGROUND
  EMT or transformation to the mesenchymal phenotype plays an important role in tumor invasion and metastasis. In vitro data suggest that mesenchymal transformation may correlate with the activation of PI3 kinase and Ras/Erk pathways. We investigated the expression of EMT markers (low E-cadherin, high fibronectin, and vimentin) and their association with p-Erk in resected pancreatic cancer.
  
  
  METHODS
  Clinical data/surgical specimens from 34 consecutive pancreatic cancer patients (pts) who underwent pancreatectomy were included. Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissues using monoclonal antibodies against vimentin, fibronectin, E-cadherin, and p-Erk. 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, Fisher's exact test) and Kendall's tau were performed at a significance level of 0.05.
  
  
  RESULTS
  The patient population was formed from 13 males and 21 females, with a median age of 66 years (range 38-84 years); American Joint Committee on Cancer (AJCC) stage 1 (n = 2), 2 (n = 27), 3 (n = 5); histological grade 1 (n = 4), 2 (n = 13), 3 (n = 16), 4 (n = 1). Median survival was 15 months (95% CI: 11-24 months). Fibronectin overexpression correlated with the presence of vimentin (p = 0.0048) and activated Erk (p = 0.0264). There was a borderline association of fibronectin with worsening grade (p = 0.06). A negative association between vimentin and E-cadherin was noted (p = 0.0024). Increased fibronectin or vimentin and decreased E-cadherin correlated with poor survival.
  
  
  CONCLUSIONS
  EMT is associated with poor survival in surgically resected pancreatic adenocarcinoma. A correlation between activated Erk and fibronectin was identified that may open avenues for targeted therapy for this subgroup.
authors: Department of Gastrointestinal Medical Oncology, UT-MD Anderson Cancer Center, Unit 426, 1515 Holcombe Ave, Houston, TX 77030, USA. mjavle@mdanderson.org
authors: M M
authors: MM
authors: Javle
authors: J F
authors: JF
authors: Gibbs
authors: K K
authors: KK
authors: Iwata
authors: Y
authors: Y
authors: Pak
authors: P
authors: P
authors: Rutledge
authors: J
authors: J
authors: Yu
authors: J D
authors: JD
authors: Black
authors: D
authors: D
authors: Tan
authors: T
authors: T
authors: Khoury
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology* / Q000601:surgery; D010766:Phosphorylation; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; D005353:Fibronectins; D014746:Vimentin; D048049:Extracellular Signal-Regulated MAP Kinases