Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations

Introduction: Double occurrence of TTF1 and ΔNp63/p40 (henceforth, p40) within the same individual cells is exceedingly rare in lung cancer. Little is known on their biological and clinical implications. Methods: Two index cases immunoreactive for both p40 and TTF1 and nine tumors selected from The...

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Autores principales:	Giuseppe Pelosi, MD, MIAC, Matteo Bulloni, PhD, Martina Vescio, PhD, Silvia Uccella, MD, Fabien Forest, MD, Giorgia Leone, MD, Massimo Barberis, MD, Daoud Rahal, MD, Paola Bossi, MD, Giovanna Finzi, MD, Deborah Marchiori, MD, Marco De Luca, MD, Fausto Sessa, MD, Sergio Harari, MD, Manuela Spinelli, MD, Patrizia Viola, MD, Paolo Macrì, MD, Stefania Maria, MD, Antonio Rizzo, MD, Antonio Picone, MD, Linda Pattini, PhD
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	ΔNp63/p40 TTF-1 Lung Non–small cell carcinoma Prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/b5599054993748b39c6aa8019d597ff7
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spelling	oai:doaj.org-article:b5599054993748b39c6aa8019d597ff72021-12-02T05:03:44ZCoexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations2666-364310.1016/j.jtocrr.2021.100222https://doaj.org/article/b5599054993748b39c6aa8019d597ff72021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666364321000813https://doaj.org/toc/2666-3643Introduction: Double occurrence of TTF1 and ΔNp63/p40 (henceforth, p40) within the same individual cells is exceedingly rare in lung cancer. Little is known on their biological and clinical implications. Methods: Two index cases immunoreactive for both p40 and TTF1 and nine tumors selected from The Cancer Genome Atlas (TCGA) according to the mRNA levels of the two relevant genes entered the study. Results: The two index cases were peripherally located, poorly differentiated, and behaviorally unfavorable carcinomas, which shared widespread p40 and TTF1 decoration within the same individual tumor cells. They also retained SMARCA2 and SMARCA4 expression, while variably stained for p53, cytokeratin 5, and programmed death-ligand 1. A subset of basal cells p40+/TTF1+ could be found in normal distal airways. Biphenotypic glandular and squamous differentiation was unveiled by electron microscopy, along with EGFR, RAD51B, CCND3, or NF1 mutations and IGF1R, MYC, CCND1, or CDK2 copy number variations on next-generation sequencing analysis. The nine tumors from TCGA (0.88% of 1018 tumors) shared the same poor prognosis, clinical presentation, and challenging histology and had activated pathways of enhanced angiogenesis and epithelial-mesenchymal transition. Mutation and copy number variation profiles did not differ from the other TCGA tumors. Conclusions: Double p40+/TTF1+ lung carcinomas are aggressive and likely underrecognized non–small cell carcinomas, whose origin could reside in double-positive distal airway stem-like basal cells through either de novo-basal-like or differentiating cell mechanisms according to a model of epithelial renewal.Giuseppe Pelosi, MD, MIACMatteo Bulloni, PhDMartina Vescio, PhDSilvia Uccella, MDFabien Forest, MDGiorgia Leone, MDMassimo Barberis, MDDaoud Rahal, MDPaola Bossi, MDGiovanna Finzi, MDDeborah Marchiori, MDMarco De Luca, MDFausto Sessa, MDSergio Harari, MDManuela Spinelli, MDPatrizia Viola, MDPaolo Macrì, MDStefania Maria, MDAntonio Rizzo, MDAntonio Picone, MDLinda Pattini, PhDElsevierarticleΔNp63/p40TTF-1LungNon–small cell carcinomaPrognosisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJTO Clinical and Research Reports, Vol 2, Iss 11, Pp 100222- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ΔNp63/p40 TTF-1 Lung Non–small cell carcinoma Prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	ΔNp63/p40 TTF-1 Lung Non–small cell carcinoma Prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Giuseppe Pelosi, MD, MIAC Matteo Bulloni, PhD Martina Vescio, PhD Silvia Uccella, MD Fabien Forest, MD Giorgia Leone, MD Massimo Barberis, MD Daoud Rahal, MD Paola Bossi, MD Giovanna Finzi, MD Deborah Marchiori, MD Marco De Luca, MD Fausto Sessa, MD Sergio Harari, MD Manuela Spinelli, MD Patrizia Viola, MD Paolo Macrì, MD Stefania Maria, MD Antonio Rizzo, MD Antonio Picone, MD Linda Pattini, PhD Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations
description	Introduction: Double occurrence of TTF1 and ΔNp63/p40 (henceforth, p40) within the same individual cells is exceedingly rare in lung cancer. Little is known on their biological and clinical implications. Methods: Two index cases immunoreactive for both p40 and TTF1 and nine tumors selected from The Cancer Genome Atlas (TCGA) according to the mRNA levels of the two relevant genes entered the study. Results: The two index cases were peripherally located, poorly differentiated, and behaviorally unfavorable carcinomas, which shared widespread p40 and TTF1 decoration within the same individual tumor cells. They also retained SMARCA2 and SMARCA4 expression, while variably stained for p53, cytokeratin 5, and programmed death-ligand 1. A subset of basal cells p40+/TTF1+ could be found in normal distal airways. Biphenotypic glandular and squamous differentiation was unveiled by electron microscopy, along with EGFR, RAD51B, CCND3, or NF1 mutations and IGF1R, MYC, CCND1, or CDK2 copy number variations on next-generation sequencing analysis. The nine tumors from TCGA (0.88% of 1018 tumors) shared the same poor prognosis, clinical presentation, and challenging histology and had activated pathways of enhanced angiogenesis and epithelial-mesenchymal transition. Mutation and copy number variation profiles did not differ from the other TCGA tumors. Conclusions: Double p40+/TTF1+ lung carcinomas are aggressive and likely underrecognized non–small cell carcinomas, whose origin could reside in double-positive distal airway stem-like basal cells through either de novo-basal-like or differentiating cell mechanisms according to a model of epithelial renewal.
format	article
author	Giuseppe Pelosi, MD, MIAC Matteo Bulloni, PhD Martina Vescio, PhD Silvia Uccella, MD Fabien Forest, MD Giorgia Leone, MD Massimo Barberis, MD Daoud Rahal, MD Paola Bossi, MD Giovanna Finzi, MD Deborah Marchiori, MD Marco De Luca, MD Fausto Sessa, MD Sergio Harari, MD Manuela Spinelli, MD Patrizia Viola, MD Paolo Macrì, MD Stefania Maria, MD Antonio Rizzo, MD Antonio Picone, MD Linda Pattini, PhD
author_facet	Giuseppe Pelosi, MD, MIAC Matteo Bulloni, PhD Martina Vescio, PhD Silvia Uccella, MD Fabien Forest, MD Giorgia Leone, MD Massimo Barberis, MD Daoud Rahal, MD Paola Bossi, MD Giovanna Finzi, MD Deborah Marchiori, MD Marco De Luca, MD Fausto Sessa, MD Sergio Harari, MD Manuela Spinelli, MD Patrizia Viola, MD Paolo Macrì, MD Stefania Maria, MD Antonio Rizzo, MD Antonio Picone, MD Linda Pattini, PhD
author_sort	Giuseppe Pelosi, MD, MIAC
title	Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations
title_short	Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations
title_full	Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations
title_fullStr	Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations
title_full_unstemmed	Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations
title_sort	coexpression of δnp63/p40 and ttf1 within most of the same individual cells identifies life-threatening nsclc featuring squamous and glandular biphenotypic differentiation: clinicopathologic correlations
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/b5599054993748b39c6aa8019d597ff7
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Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations

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