title: Circulating tumor cells and EpCAM expression in neuroendocrine tumors.
abstract: OBJECTIVE
  Neuroendocrine tumors (NET) are heterogeneous tumors with widely variable survival. It is unknown whether they express EpCAM (epithelial cell adhesion molecule) and thus whether NET circulating tumor cells (CTC) are detectable. We systematically investigated EpCAM expression and CTC detection in patients with metastatic NETs and evaluated the potential of CTCs to predict radiological progression.
  
  
  METHODS
  EpCAM protein expression was evaluated in 74 samples of formalin-fixed, paraffin-embedded NET tissue by immunohistochemistry. Seventy-nine patients with metastatic NETs (42 midgut, 5 unknown primary, 19 pancreatic, 13 bronchopulmonary) had blood samples drawn for CTC isolation and enumeration utilizing the CellSearch platform. Patients were classified as having progressive or nonprogressive disease on the basis of serial imaging.
  
  
  RESULTS
  Strong homogeneous, membranous EpCAM expression was observed in all ileal (n = 26) and pancreatic NETs (n = 16), whereas variable EpCAM expression was observed in bronchopulmonary NETs (n = 13). Forty-three percent of midgut and 21% of pancreatic NETs had CTCs detected with a range of 0-62 and 0-11, respectively. The absence of CTCs was strongly associated with stable disease (P < 0.001). There was a moderate correlation between CTC levels and urinary 5-hydroxyindole acetic acid (r = 0.5, P = 0.007) and between CTC levels and burden of liver metastases (B = 8.91, P < 0.001). There was no or low correlation between CTC levels and Ki-67 (r = 0.08, P = 0.59) and serum chromogranin A (r = 0.246, P = 0.03).
  
  
  CONCLUSIONS
  This is the first systematic analysis showing EpCAM expression and CTC detection in NETs. CTCs seem to be associated with progressive disease and may provide useful prognostic information given the variable survival rates in these tumors.
authors.affiliation: Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital, UCL Cancer Institute, University College London, London, United Kingdom.
authors.forename: Mohid S
authors.initials: MS
authors.lastname: Khan
authors.forename: Theodora
authors.initials: T
authors.lastname: Tsigani
authors.forename: Mohammed
authors.initials: M
authors.lastname: Rashid
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Rabouhans
authors.forename: Dominic
authors.initials: D
authors.lastname: Yu
authors.forename: Tu Vinh
authors.initials: TV
authors.lastname: Luong
authors.forename: Martyn
authors.initials: M
authors.lastname: Caplin
authors.forename: Tim
authors.initials: T
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018450:Disease Progression; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000097:blood* / Q000000981:diagnostic imaging / Q000378:metabolism; D016612:Paraffin Embedding; D011859:Radiography
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule