title: Preoperative circulating tumor cell detection using the isolation by size of epithelial tumor cell method for patients with lung cancer is a new prognostic biomarker.
abstract: OBJECTIVE
  Pathologic TNM staging is currently the best prognostic factor for non-small cell lung carcinoma (NSCLC). However, even in early-stage NSCLC, the recurrence rates after surgery range from 25% to 50%. The preoperative detection of circulating tumor cells (CTC) could be useful to tailor new therapeutic strategies in NSCLC. We assessed the presence of CTC in NSCLC patients undergoing surgery, using cytologic analyses, after their isolation by size of epithelial tumor cells (ISET method). The presence and the number of CTCs were considered and correlated with clinicopathologic parameters including patient follow-up.
  
  
  METHODS
  Of the 247 blood samples tested, 208 samples were from patients with resectable NSCLC and 39 from healthy subjects. The mean follow-up was 24 months. An image of detected cells with presumably nonhematologic features [initially defined as "circulating nonhematologic cells" (CNHC)] was recorded. The presence of CNHC was assessed blindly and independently by 10 cytopathologists, using cytologic criteria of malignancy on stained filters. The count of detected CNHCs was made for each filter.
  
  
  RESULTS
  One hundred two of 208 (49%) patients showed CNHCs corresponding to CNHC with malignant cytopathologic features in 76 of 208 (36%) cases. CNHCs were not detected in the control group. A level of 50 or more CNHCs corresponding to the third quartile was associated with shorter overall and disease-free-survival, independently of disease staging, and with a high risk of recurrence and death in early-stage I + II-resectable NSCLC.
  
  
  CONCLUSIONS
  A high percentage of NSCLC patients show preoperative detection of CNHC by the ISET method. The presence and level of 50 or more CNHCs are associated with worse survival of patients with resectable NSCLC.
authors.affiliation: INSERM (Institut National de Santé et de Recherche Médicale) ERI-21, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Hofman
authors.forename: Christelle
authors.initials: C
authors.lastname: Bonnetaud
authors.forename: Marius I
authors.initials: MI
authors.lastname: Ilie
authors.forename: Philippe
authors.initials: P
authors.lastname: Vielh
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Vignaud
authors.forename: Jean François
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lantuejoul
authors.forename: Eric
authors.initials: E
authors.lastname: Piaton
authors.forename: Nadine
authors.initials: N
authors.lastname: Mourad
authors.forename: Catherine
authors.initials: C
authors.lastname: Butori
authors.forename: Eric
authors.initials: E
authors.lastname: Selva
authors.forename: Michel
authors.initials: M
authors.lastname: Poudenx
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Sibon
authors.forename: Sabrina
authors.initials: S
authors.lastname: Kelhef
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vénissac
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jais
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mouroux
authors.forename: Thierry Jo
authors.initials: TJ
authors.lastname: Molina
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D057234:Preoperative Period
chemical_list: D014408:Biomarkers, Tumor