title: Tumor markers in lung cancer: does the method of obtaining the cut-off point and reference population influence diagnostic yield?
abstract: OBJECTIVE
  The aim of this study was to evaluate the clinical usefulness of the tumor markers CA125, CEA, NSE, SCC, and TPS in a group of patients with lung cancer. We estimated the influence of the method for choosing the cut-off point and of considering as a reference population either healthy controls or patients with some form of non-neoplastic pulmonary disease (NNPD).
  
  
  METHODS
  The tumor markers were determined using enzyme immunoassay techniques, and their diagnostic yield was evaluated using ROC curves and their correlation with the percentages between false and true positives. The diagnostic parameters of the tumor markers are presented in 116 patients with lung cancer and compared with a group of 25 healthy controls and another group of 80 patients with some form of NNPD. We determined on the one hand the cut-off points resulting from the best sensitivity-specificity balance in the ROC curves and on the other those resulting from considering a specificity of 95%. With the two cut-offs we studied the different diagnostic parameters: sensitivity, specificity and accuracy or area below the ROC curve.
  
  
  RESULTS
  Optimum diagnostic yield is obtained when we choose the cut-off point determined by the best balance of sensitivity and specificity in the ROC curves and take a healthy population as a reference group. The cut-off values for CA125, CEA, NSE, SCC, and TPS were 24 U/mL, 2.8 ng/mL, 9.8 ng/mL, 1.6 ng/mL, and 67.8 U/L, respectively.
  
  
  CONCLUSIONS
  Our results suggest that in future studies on tumor markers, a group of healthy subjects should be used as a reference population and ROC curves should be used to obtain the optimum cut-offs.
authors.affiliation: Clinical Analysis Unit, Virgen de la Arrixaca University Hospital, Murcia, Spain. mlealh@papps.org
authors.forename: T C
authors.initials: TC
authors.lastname: Pina
authors.forename: I T
authors.initials: IT
authors.lastname: Zapata
authors.forename: J B
authors.initials: JB
authors.lastname: López
authors.forename: J L
authors.initials: JL
authors.lastname: Pérez
authors.forename: P P
authors.initials: PP
authors.lastname: Paricio
authors.forename: P M
authors.initials: PM
authors.lastname: Hernández
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D005069:Evaluation Studies as Topic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D010751:Phosphopyruvate Hydratase / Q000097:blood; D012372:ROC Curve; D012016:Reference Values; D012680:Sensitivity and Specificity; D015843:Serpins
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D002272:Carcinoembryonic Antigen; D010455:Peptides; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; C089984:tissue polypeptide specific antigen; D010751:Phosphopyruvate Hydratase