title: A comprehensive immunohistochemistry algorithm for the histological subtyping of small biopsies obtained from non-small cell lung cancers.
abstract: OBJECTIVE
  Need for accurate histologic subtyping of non-small cell lung carcinomas (NSCLCs) is growing. IHC patterns may be ambiguous in some cases, rendering it difficult to determine subtypes.
  
  
  RESULTS
  Tissue microarrays composed of 184 resected NSCLCs were stained for TTF-1, Napsin A, CK7, p40, p63, CK5/6, and mucicarmine. TTF-1 and Napsin A were chosen as the most accurate adenocarcinoma (ADC) marker (ACM), and p40 as squamous cell carcinoma (SCC) marker (SCM). We then prospectively performed IHC using these markers (TTF-1, Napsin A, and p40) in a cohort of small NSCLC biopsies (n = 186) with ambiguous morphology. Of these biopsies, 82.8% (154/186) were classifiable into either ADC or SCC by applying '3-marker IHC panel'. Additional CK7, p63, and CK5/6 were applied in 30 biopsies with equivocal IHC patterns, including 18 ACM-/SCM- (double-negative) and 12 ACM+/SCM+ (double-positive) cases. Decision tree and support vector machine models revealed that TTF-1 was a critical single marker for ADC in double-positive cases (91.7% accuracy), whereas p63 and/or CK5/6 helped to subtype double-negative cases (72.2% accuracy).
  
  
  CONCLUSIONS
  We propose a novel comprehensive algorithm for subtyping NSCLCs using a 3-marker IHC panel and additional p63 and CK5/6 that would be useful for subtyping small NSCLC biopsies.
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jaemoon
authors.initials: J
authors.lastname: Koh
authors.forename: Heounjeong
authors.initials: H
authors.lastname: Go
authors.forename: Moon-Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Jin-Haeng
authors.initials: JH
authors.lastname: Chung
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification* / Q000473:pathology*; D003663:Decision Trees; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000145:classification* / Q000473:pathology*; D012680:Sensitivity and Specificity; D060388:Support Vector Machine; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor
keywords: Napsin A and p40 panel; TTF-1; algorithm; biopsy specimens; histologic subtyping; immunohistochemistry; non-small cell carcinoma