title: Large-scale comparative analyses of immunomarkers for diagnostic subtyping of non-small-cell lung cancer biopsies.
abstract: OBJECTIVE
  Patient stratification according to histological subtype is important for non-small-cell lung cancer (NSCLC) therapy. For specimens with uncertain histomorphology, rational and material-saving algorithms for specific and sensitive immunotyping need to be established.
  
  
  RESULTS
  One thousand one hundred and forty-five NSCLCs were immunohistochemically investigated for the expression of cytokeratin 5/6 (CK5/6), CK7, thyroid transcription factor-1 (TTF-1), p63, napsin-A, and desmocollin-3. Overall, napsin-A and desmocollin-3 were the most specific markers (specificity of each, 99%), and CK7 and CK5/6 the most sensitive markers (sensitivity, 96% and 94%) for adenocarcinomatous and squamous differentiation, respectively. However, for NSCLC not otherwise specified (NOS) cases, TTF-1, p63, CK5/6 and CK7 were found to be the most reliable markers. On the basis of morphology alone, approximately two-thirds of all NSCLCs could be reliably diagnosed in biopsy specimens. Immunohistochemistry further reduced the NOS fraction to 10%.
  
  
  CONCLUSIONS
  When morphology alone is not reliable, the use of selected markers and marker panels is highly sensitive and specific, and allows reliable distinction between squamous cell carcinoma and adenocarcinoma. Considering the impact of typing for the selection of molecular testing and treatment response, one must be aware of immunomarker expression patterns in NSCLC and their diagnostic value, in order to optimize typing and thereby maximize patient benefit from chemotherapy.
authors.affiliation: Institute for Pathology, University Hospital Heidelberg, Heidelberg, Germany. arne.warth@med.uni-heidelberg.de
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
authors.forename: Felix J F
authors.initials: FJ
authors.lastname: Herth
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Hans
authors.initials: H
authors.lastname: Hoffmann
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Schnabel
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification* / Q000175:diagnosis* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D003937:Diagnosis, Differential; D006801:Humans; D053555:Keratin-5 / Q000378:metabolism; D053553:Keratin-6 / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism; D008175:Lung Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; C081876:CKAP4 protein, human; D053555:Keratin-5; D053553:Keratin-6; D053552:Keratin-7; D008565:Membrane Proteins; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors