title: Gene expression profiling reveals GC and CEACAM1 as new tools in the diagnosis of lung carcinoids.
abstract: BACKGROUND
  Classification of lung carcinoids into typical and atypical is a diagnostic challenge since no immunohistochemical tools are available to support pathologists in distinguishing between the two subtypes. A differential diagnosis is essential for clinicians to correctly discuss therapy, prognosis and follow-up with patients. Indeed, the distinction between the two typical and atypical subtypes on biopsies/cytological specimens is still unfeasible and sometimes limited also after radical surgeries. By comparing the gene expression profile of typical (TC) and atypical carcinoids (AC), we intended to find genes specifically expressed in one of the two subtypes that could be used as diagnostic markers.
  
  
  METHODS
  Expression profiling, with Affymetrix arrays, was performed on six typical and seven atypical samples. Data were validated on an independent cohort of 29 tumours, by means of quantitative PCR and immunohistochemistry (IHC).
  
  
  RESULTS
  High-throughput gene expression profiling was successfully used to identify a gene signature specific for atypical lung carcinoids. Among the 273 upregulated genes in the atypical vs typical subtype, GC (vitamin D-binding protein) and CEACAM1 (carcinoembryonic antigen family member) emerged as potent diagnostic markers. Quantitative PCR and IHC on a validation set of 17 ACs and 12 TCs confirmed their reproducibility and feasibility.
  
  
  CONCLUSIONS
  GC and CEACAM1 can distinguish between TC and AC, defining an IHC assay potentially useful for routine cytological and histochemical diagnostic procedures. The high sensitivity and reproducibility of this new diagnostic algorithm strongly support a further validation on a wider sample size.
authors: Division of Medical Oncology of the Respiratory Tract, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors: F
authors: F
authors: Toffalorio
authors: Department of Experimental Oncology, Molecular Medicine for Care Program, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors: E
authors: E
authors: Belloni
authors: Histopatology and Molecular Diagnostics Unit, Pathology Division, European Institute of Oncology, Milan, Italy.
authors: M
authors: M
authors: Barberis
authors: Center of Genomic Science of IIT@SEMM, Milan, Italy.
authors: G
authors: G
authors: Bucci
authors: Real Time PCR Service, FIRC Institute of Molecular Oncology Foundation, Milan, Italy.
authors: L
authors: L
authors: Tizzoni
authors: 1] Pathology Division, European Institute of Oncology, Milan, Italy [2] University of Milan, School of Medicine, Milan, Italy.
authors: G
authors: G
authors: Pruneri
authors: Histopatology and Molecular Diagnostics Unit, Pathology Division, European Institute of Oncology, Milan, Italy.
authors: C
authors: C
authors: Fumagalli
authors: Division of Medical Oncology of the Respiratory Tract, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors: G
authors: G
authors: Spitaleri
authors: Division of Medical Oncology of the Respiratory Tract, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors: C
authors: C
authors: Catania
authors: Department of Pathology and Laboratory Medicine, Fondazione IRCCS National Cancer Institute, Milan, Italy.
authors: F
authors: F
authors: Melotti
authors: 1] Department of Experimental Oncology, Molecular Medicine for Care Program, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy [2] University of Milan, School of Medicine, Milan, Italy.
authors: P G
authors: PG
authors: Pelicci
authors: 1] University of Milan, School of Medicine, Milan, Italy [2] Thoracic Surgery Division, European Institute of Oncology, Milan, Italy.
authors: L
authors: L
authors: Spaggiari
authors: Division of Medical Oncology of the Respiratory Tract, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors: T
authors: T
authors: De Pas
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002276:Carcinoid Tumor / Q000175:diagnosis* / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D059467:Transcriptome; D014809:Vitamin D-Binding Protein / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D014809:Vitamin D-Binding Protein