title: Morphological analysis of circulating tumour cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method.
abstract: OBJECTIVE
  Recurrence rates after surgery for non-small cell lung cancer (NSCLC) range from 25 to 50% and 5-year survival is only 60-70%. Because no biomarkers are predictive of recurrence or the onset of metastasis, pathological TNM (pTNM) staging is currently the best prognostic factor. Consequently, the preoperative detection of circulating tumour cells (CTCs) might be useful in tailoring therapy. The aim of this study was to characterize morphologically any circulating non-haematological cells (CNHCs) in patients undergoing surgery for NSCLC using the isolation by size of epithelial tumour cell (ISET) method.
  
  
  METHODS
  Of 299 blood samples tested, 250 were from patients with resectable NSCLC and 59 from healthy controls. The presence of CNHCs was assessed blindly and independently by 10 cytopathologists on May-Grünwald-Giemsa stained filters and the cells classified into three groups: (i) malignant cells, (ii) uncertain malignant cells, and (iii) benign cells. We assessed interobserver agreement using Kappa (κ) analysis as the measure of agreement.
  
  
  RESULTS
  A total of 123 out of 250 (49%) patients showed CNHCs corresponding to malignant, uncertain malignant and benign cells, in 102/250 (41%), 15/250 (6%) and 6/250 (2%) cases, respectively. No CNHCs were detected in the blood of healthy subjects. Interobserver diagnostic variability was absent for CNHCs, low for malignant cells and limited for uncertain malignant and benign cells.
  
  
  CONCLUSIONS
  Identification of CTCs in resectable NSCLC patients, using ISET technology and according to cytopathological criteria of malignancy, appears to be a new and promising field of cytopathology with potential relevance to lung oncology.
authors.affiliation: EA 4319, Faculty of Medicine, University of Nice Sophia Antipolis, Nice, France.
authors.forename: V
authors.initials: V
authors.lastname: Hofman
authors.forename: E
authors.initials: E
authors.lastname: Long
authors.forename: M
authors.initials: M
authors.lastname: Ilie
authors.forename: C
authors.initials: C
authors.lastname: Bonnetaud
authors.forename: J M
authors.initials: JM
authors.lastname: Vignaud
authors.forename: J F
authors.initials: JF
authors.lastname: Fléjou
authors.forename: S
authors.initials: S
authors.lastname: Lantuejoul
authors.forename: E
authors.initials: E
authors.lastname: Piaton
authors.forename: N
authors.initials: N
authors.lastname: Mourad
authors.forename: C
authors.initials: C
authors.lastname: Butori
authors.forename: E
authors.initials: E
authors.lastname: Selva
authors.forename: C H
authors.initials: CH
authors.lastname: Marquette
authors.forename: M
authors.initials: M
authors.lastname: Poudenx
authors.forename: S
authors.initials: S
authors.lastname: Sibon
authors.forename: S
authors.initials: S
authors.lastname: Kelhef
authors.forename: N
authors.initials: N
authors.lastname: Vénissac
authors.forename: J P
authors.initials: JP
authors.lastname: Jais
authors.forename: J
authors.initials: J
authors.lastname: Mouroux
authors.forename: T J
authors.initials: TJ
authors.lastname: Molina
authors.forename: P
authors.initials: P
authors.lastname: Vielh
authors.forename: P
authors.initials: P
authors.lastname: Hofman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000473:pathology*; D016022:Case-Control Studies; D002469:Cell Separation / Q000379:methods*; D048429:Cell Size; D003581:Cytodiagnosis / Q000379:methods*; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*