Cell of origin markers identify different prognostic subgroups of lung adenocarcinoma Academic Article uri icon


MeSH Major

  • Neoplasms
  • Xenograft Model Antitumor Assays


  • 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.

publication date

  • May 2018



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.humpath.2018.01.017

PubMed ID

  • 29409837

Additional Document Info

start page

  • 167

end page

  • 178


  • 75