title: Utility of 10 immunohistochemical markers including novel markers (desmocollin-3, glypican 3, S100A2, S100A7, and Sox-2) for differential diagnosis of squamous cell carcinoma from adenocarcinoma of the Lung.
abstract: BACKGROUND
  Recent clinical trials revealed that accurate histologic typing of non-small cell lung cancer, especially squamous cell carcinoma (SCC), is essential.
  
  
  METHODS
  We analyzed 10 antibodies expression in 150 SCC cases (53 well-, 51 moderately, and 46 poorly differentiated cases) and 159 adenocarcinoma (AC) cases (49 well-, 52 moderately, and 58 poorly differentiated cases).
  
  
  RESULTS
  In all SCC and AC cases, p63 was the most sensitive marker for SCC (98.7%), followed by high-molecular-weight (HM) cytokeratin (CK) (97.3%), CK5/6 (93.3%), Sox2 (80%), thrombomodulin (79.3%), desmocollin-3 (72.7%), S100A7 (70.7%), S100A2 (63.3%), and glypican-3 (46.7%). Desmocollin-3 was the most specific marker for SCC (100%), followed by CK5/6 (98%), Sox2 (95.5%), glypican-3 (92.4%), S100A7 (86.8%), thrombomodulin (79.9%), S100A2 (64.6%), p63 (51.6%), and HMCK (33.3%). Thyroid transcription factor-1 (TTF-1) expression was observed in 87.4% of AC cases and 2.0% of SCC cases. When analyzing only poorly differentiated tumors, HMCK was the most sensitive marker for SCC (100%), followed by p63 (97.8%), CK5/6 (87.0%), Sox2 (71.7%), thrombomodulin (58.7%), desmocollin-3 (52.2%), S100A2 (50%), glypican-3 (45.7%), and S100A7 (45.7%). Desmocollin-3 was the most specific marker for poorly differentiated SCC (100%), followed by CK5/6 (98.3%), glypican-3 (94.8%), Sox2 (94.8%), S100A2 (81%), S100A7 (75.9%), thrombomodulin (72.4%), p63 (48.3%), and HMCK (36.8%). The 10-fold crossvalidated classification and regression tree analysis revealed that the combination of CK5/6 and TTF-1 was the best immunohistochemical marker panel for the differentiation between SCC and AC.
  
  
  CONCLUSIONS
  CK5/6 is the best marker for differentiating SCC and AC, irrespective of the histological grade of the tumor. Thus, the combination of CK5/6 and TTF-1 is the most recommended combination of immunohistochemical markers.
authors.affiliation: Division of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan. ktsuta@ncc.go.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Takahashi
authors.forename: Akiko M
authors.initials: AM
authors.lastname: Maeshima
authors.forename: Hisao
authors.initials: H
authors.lastname: Asamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D051187:Desmocollins / Q000378:metabolism; D003937:Diagnosis, Differential; D053673:Glypicans / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D053555:Keratin-5 / Q000378:metabolism; D053553:Keratin-6 / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D046888:Tissue Array Analysis; D014157:Transcription Factors
chemical_list: D014408:Biomarkers, Tumor; D002630:Chemotactic Factors; D004268:DNA-Binding Proteins; C490356:DSC3 protein, human; D051187:Desmocollins; C105937:GPC3 protein, human; D053673:Glypicans; D053555:Keratin-5; D053553:Keratin-6; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C098997:S100A2 protein, human; C089242:S100A7 protein, human; D055748:SOXB1 Transcription Factors; C504003:TTF1 protein, human; D014157:Transcription Factors