Cell of origin markers identify different prognostic subgroups of lung adenocarcinoma

Fabrizio Tabbò, Alessia Nottegar, Francesco Guerrera, Enrica Migliore, Claudio Luchini, Francesca Maletta, Nicola Veronese, Licia Montagna, Marcello Gaudiano, Filomena Di Giacomo, Pier Luigi Filosso, Luisa Delsedime, Giovannino Ciccone, Aldo Scarpa, Anna Sapino, Alberto Oliaro, Enrico Ruffini, Giorgio Inghirami, Marco Chilosi

Research output: Contribution to journalArticlepeer-review


Strong prognostic markers able to stratify lung adenocarcinoma (ADC) patients are lacking. We evaluated whether a six-immunohistochemical markers panel (TTF1, SP-A, Napsin A, MUC5AC, CDX2 and CK5), defining the putative neoplastic “cell of origin,” allows to identify prognostic subgroups among lung ADC. We screened a large cohort of ADC specimens (2003–2013) from Torino Institutional Repository identifying: (i) marker positivity by immunohistochemistry, (ii) main morphological appearance by light microscopy, (iii) presence of “hotspot” mutations of candidate genes by Sequenom technology. To evaluate possible predictors of survival and time to recurrence, uni- and multivariable-adjusted comparisons were performed. We identified 4 different subgroups: “alveolar,” “bronchiolar,” “mixed” and “null type." Alveolar-differentiated ADC were more common in young (P =.065), female (P =.083) patients, frequently harboring EGFR-mutated (P =.003) tumors with acinar pattern (P <.001). Bronchiolar-differentiated ADC were more associated with mucinous and solid pattern (P <.001), higher degree of vascular invasion (P =.01) and KRAS gene mutations (P =.07). Bronchiolar, mixed, and null types were independent negative predictors for overall survival, and the latter two had a shorter time to recurrence. This “Cell of Origin” classifier is more predictable than morphology and genetics and is an independent predictor of survival on a multivariate analysis.

Original languageEnglish
Pages (from-to)167-178
Number of pages12
JournalHuman Pathology
Publication statusPublished - May 1 2018


  • Biomarkers
  • Genetic mutations
  • Immunohistochemistry
  • Lung adenocarcinoma
  • Morphology
  • Survival analysis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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