title: Choice of tumour markers in patients with neuroendocrine tumours is dependent on the histological grade. A marker study of Chromogranin A, Neuron specific enolase, Progastrin-releasing peptide and cytokeratin fragments.
abstract: BACKGROUND
  Chromogranin A (CgA) is the most important tumour marker for well-differentiated neuroendocrine tumours (NET) and neuron specific enolase (NSE) for poorly differentiated neuroendocrine carcinoma (NEC). This study investigated whether the markers progastrin-releasing peptide (proGRP) and cytokeratin fragments (CKfr) CK8, CK18 and CK19 (MonoTotal) can be of additional value to the histological classification and help predict survival in these patients.
  
  
  METHODS
  CgA, NSE, proGRP and CKfr were measured in 242 patients with grade 1 NET (G1NET), 38 with grade 2 NET (G2NET), 42 with large cell NEC (LCNEC), 251 with small cell NEC (SCNEC) and in 282 healthy persons. Results were compared with tumour characteristics and survival by means of Receiver Operating Characteristics (ROC) curves and Cox regression analyses.
  
  
  RESULTS
  The largest area under the ROC curve was for CgA (0.86, 0.91 and 0.90, respectively) when comparing patients with G1NET, G2NET and LCNEC with healthy persons. ProGRP showed the highest sensitivity (73%) at 95% specificity in patients with SCNEC. In a multivariate survival analysis, only CKfr was associated with survival (P<0.0001) for patients with well-differentiated NET (G1NET and G2NET). For patients with poorly differentiated NEC, both CKfr and NSE were associated with survival (P<0.0001 and P=0.003, respectively).
  
  
  CONCLUSIONS
  Within all histological groups a combination of tumour markers proved to be more informative as diagnostic and prognostic marker than each marker alone. In patients with well-differentiated NET and LCNEC we recommend the use of CgA and CKfr, whilst in patients with SCNEC, proGRP and CKfr are preferred.
authors.affiliation: Department of Clinical Chemistry, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, PO Box 90203, 1006 BE Amsterdam, The Netherlands. t.korse@nki.nl
authors.forename: Catharina M
authors.initials: CM
authors.lastname: Korse
authors.forename: Babs G
authors.initials: BG
authors.lastname: Taal
authors.forename: Andrew
authors.initials: A
authors.lastname: Vincent
authors.forename: Marie-Louise F
authors.initials: ML
authors.lastname: van Velthuysen
authors.forename: Paul
authors.initials: P
authors.lastname: Baas
authors.forename: Johanna C G M
authors.initials: JC
authors.lastname: Buning-Kager
authors.forename: Theodora C
authors.initials: TC
authors.lastname: Linders
authors.forename: Johannes M G
authors.initials: JM
authors.lastname: Bonfrer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D053379:Chromogranin A / Q000097:blood*; D005260:Female; D006801:Humans; D007633:Keratins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000097:blood* / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood*; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D012372:ROC Curve; D011994:Recombinant Proteins / Q000097:blood; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A; D010446:Peptide Fragments; D011994:Recombinant Proteins; C087079:pro-gastrin-releasing peptide (31-98); D007633:Keratins; D010751:Phosphopyruvate Hydratase