title: An elevated progastrin-releasing peptide level in patients with well-differentiated neuroendocrine tumours indicates a primary tumour in the lung and predicts a shorter survival.
abstract: BACKGROUND
  Progastrin-releasing peptide (proGRP) is a recently identified biomarker of small-cell lung cancer. In well-differentiated neuroendocrine tumours (WDNETs), this study investigates the association between proGRP and tumour characteristics and the prognostic value of proGRP levels compared with chromogranin A (CgA) levels.
  
  
  METHODS
  Serum samples were obtained in 282 patients with WDNET. The receiver operating characteristic (ROC) curve technique was used to assess specificity and sensitivity in the identification of a primary tumour location. Cox proportional hazards models and Kaplan-Meier curves were constructed to determine the association of patients' characteristics and tumour markers with survival.
  
  
  RESULTS
  For proGRP, the ROC curve indicated a cut-off level of 90 ng/l (approximately twice the upper reference value), with a specificity of 99% and a sensitivity of 43% in distinguishing primary pulmonary tumours from other sites. In the multivariate Cox model, both proGRP and CgA were strongly associated with survival (P < 0.0001 for both variables).
  
  
  CONCLUSIONS
  A high-risk proGRP level (more than twice the upper reference value) in patients with WDNETs is a strong indication for a primary tumour in the lung. Besides CgA, proGRP is a complementary tumour marker for prognosis and treatment monitoring in patients with neuroendocrine tumour.
authors.affiliation: Departments of Clinical Chemistry. Electronic address: t.korse@nki.nl.
authors.forename: C M
authors.initials: CM
authors.lastname: Korse
authors.affiliation: Medical Oncology.
authors.forename: B G
authors.initials: BG
authors.lastname: Taal
authors.affiliation: Departments of Clinical Chemistry.
authors.forename: J M G
authors.initials: JMG
authors.lastname: Bonfrer
authors.affiliation: Biometrics.
authors.forename: A
authors.initials: A
authors.lastname: Vincent
authors.affiliation: Pathology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: van Velthuysen
authors.affiliation: Medical Oncology.
authors.forename: P
authors.initials: P
authors.lastname: Baas
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000097:blood*; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000401:mortality / Q000556:secondary*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018358:Neuroendocrine Tumors / Q000097:blood / Q000401:mortality / Q000556:secondary*; D016016:Proportional Hazards Models; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D019886:Gastrin-Releasing Peptide