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Hum Pathol. 2018 May;75:167-178. doi: 10.1016/j.humpath.2018.01.017. Epub 2018 Jan 31.

Cell of origin markers identify different prognostic subgroups of lung adenocarcinoma.

Author information

1
Department of Molecular Biotechnology and Health Science and Center for Experimental Research and Medical Studies, University of Torino, 10126 Torino, Italy; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10021, USA. Electronic address: fabrizio.tabbo@unito.it.
2
Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, Italy.
3
Department of Thoracic Surgery, AOU Città della Salute e della Scienza di Torino, 10126 Torino, Italy.
4
Unit of Cancer Epidemiology, AOU Città della Salute e della Scienza di Torino and CPO Piemonte, 10126 Torino, Italy.
5
Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, Italy; ARC-Net Research Center, University and Hospital Trust of Verona, 37134 Verona, Italy; Department of Pathology, Santa Chiara Hospital, 38100 Trento, Italy.
6
Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
7
National Research Council, CNR, Padua, 38121, Italy; Institute of Clinical Research and Education in Medicine, 38121 Padua, Italy.
8
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10021, USA.
9
Department of Molecular Biotechnology and Health Science and Center for Experimental Research and Medical Studies, University of Torino, 10126 Torino, Italy; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10021, USA.
10
Department of Medical Sciences, University of Torino, 10126 Torino, Italy; Candiolo Cancer Institute - FPO, IRCCS, I-10060, Candiolo (To), Italy.
11
Department of Molecular Biotechnology and Health Science and Center for Experimental Research and Medical Studies, University of Torino, 10126 Torino, Italy; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10021, USA; Department of Pathology and NYU Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
12
Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, Italy; Department of Pathology, Pederzoli Hospital, 37134 Verona, Italy.

Abstract

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.

KEYWORDS:

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

PMID:
29409837
DOI:
10.1016/j.humpath.2018.01.017
[Indexed for MEDLINE]

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