title: ΔNp63 (p40) and thyroid transcription factor-1 immunoreactivity on small biopsies or cellblocks for typing non-small cell lung cancer: a novel two-hit, sparing-material approach.
abstract: BACKGROUND
  Diagnosing non-small cell lung cancer on biopsy/cellblock samples by morphology may be demanding. As sparing material for molecular testing is mandatory, a minimalist immunohistochemistry (IHC)-based diagnostic approach is warranted by means of novel, reliable, and easy-to-assess biomarkers.
  
  
  METHODS
  Forty-six consecutive biopsy/cellblock samples and the corresponding resection specimens (as the gold standard for morphology and IHC) from 30 adenocarcinomas (AD), 10 squamous carcinomas (SQC), 5 adenosquamous carcinomas (ADSQC), and 1 sarcomatoid carcinoma (SC) were IHC-evaluated for p40 [corresponding to nontransactivating ΔNp63 isoforms] and thyroid transcription factor-1 (TTF1) by semiquantitative assessment. For p40, also immunodecoration intensity was taken into account and dichotomized as strong or low.
  
  
  RESULTS
  Nonrandom and overlapping distributions of the relevant markers were found in biopsy/cellblock and surgical specimens, which closely correlated with each other and the diverse tumor categories, with no differences in area under curve-receiver-operating-characteristic curves for each marker between any two samples, including p40 and p63. Diagnostic combinations were p40-/TTF1+ or TTF1- for AD (where p40 was negative, apart from 5/30 AD showing at the best 1-2% tumor cells with low intensity); p40+/TTF1- (p40 strong and by far higher than 50%) for SQC; and p40+/TTF1+ or p40+/TTF1- (p40 strong and less than 50%) for ADSQC. The single SC case was p40-/TTF1-, suggesting glandular lineage. Practically, 41/46 (89%) tumors were correctly classified by IHC on small samples, including 30 AD, 10 SQC, 1/5 ADSQC, and no SC. Underdiagnosis of ADSQC was actually because of sampling error of biopsies/cellblocks rather than insufficient biomarker robustness, whereas underdiagnosis of SC was really because of the failure of either marker to highlight epithelial-mesenchymal transition.
  
  
  CONCLUSIONS
  This minimalist IHC-based model of p40 and TTF1 on biopsy/cellblock samples was effective to correctly subtype most cases of lung cancer.
authors.affiliation: Department of Pathology and Laboratory Medicine,Fondazione IRCCS National Cancer Institute, Milan, Italy. giuseppe.pelosi@istitutotumori.mi.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pelosi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabbri
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bianchi
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbareschi
authors.forename: Paolo
authors.initials: P
authors.lastname: Graziano
authors.forename: Alberto
authors.initials: A
authors.lastname: Cavazza
authors.forename: Natasha
authors.initials: N
authors.lastname: Rekhtman
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.forename: Paolo
authors.initials: P
authors.lastname: Scanagatta
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D018196:Carcinoma, Adenosquamous / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification* / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000145:classification* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C115051:TP63 protein, human; C504003:TTF1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins