title: Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma.
abstract: OBJECTIVE
  We assessed circulating tumor cells (CTCs) with epithelial and mesenchymal phenotypes as a potential prognostic biomarker for patients with pancreatic adenocarcinoma (PDAC).
  
  
  BACKGROUND
  PDAC is the fourth leading cause of cancer death in the United States. There is an urgent need to develop biomarkers that predict patient prognosis and allow for better treatment stratification.
  
  
  METHODS
  Peripheral and portal blood samples were obtained from 50 patients with PDAC before surgical resection and filtered using the Isolation by Size of Epithelial Tumor cells method. CTCs were identified by immunofluorescence using commercially available antibodies to cytokeratin, vimentin, and CD45.
  
  
  RESULTS
  Thirty-nine patients (78%) had epithelial CTCs that expressed cytokeratin but not CD45. Twenty-six (67%) of the 39 patients had CTCs which also expressed vimentin, a mesenchymal marker. No patients had cytokeratin-negative and vimentin-positive CTCs. The presence of cytokeratin-positive CTCs (P < 0.01), but not mesenchymal-like CTCs (P = 0.39), was associated with poorer survival. The presence of cytokeratin-positive CTCs remained a significant independent predictor of survival by multivariable analysis after accounting for other prognostic factors (P < 0.01). The detection of CTCs expressing both vimentin and cytokeratin was predictive of recurrence (P = 0.01). Among patients with cancer recurrence, those with vimentin-positive and cytokeratin-expressing CTCs had decreased median time to recurrence compared with patients without CTCs (P = 0.02).
  
  
  CONCLUSIONS
  CTCs are an exciting potential strategy for understanding the biology of metastases, and provide prognostic utility for PDAC patients. CTCs exist as heterogeneous populations, and assessment should include phenotypic identification tailored to characterize cells based on epithelial and mesenchymal markers.
authors.affiliation: *Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD†Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD‡Department of Medical Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD§Department of Radiation Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD¶Department of Gastroenterology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD||Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Katherine E
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mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000097:blood; D017493:Leukocyte Common Antigens / Q000097:blood; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000601:surgery*; D010641:Phenotype; D011379:Prognosis; D015996:Survival Rate; D014746:Vimentin / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D014746:Vimentin; D007633:Keratins; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human