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

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

JTO Clinical and Research Reports (Nov 2021)

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

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

Affiliations

Giuseppe Pelosi, MD, MIAC: Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Inter-Hospital Pathology Division, Istituto di Ricovero e Cura a Carattere Scientifico (IRCSS) MultiMedica, Milan, Italy; Corresponding author. Address for correspondence: Giuseppe Pelosi, MD, MIAC, Inter-Hospital Pathology Division, Istituto di Ricovero e Cura a Carattere Scientifico (IRCSS) MultiMedica, Via Gaudenzio Fantoli 16/15, 20138 Milan, Italy.
Matteo Bulloni, PhD: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy
Martina Vescio, PhD: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy
Silvia Uccella, MD: Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Fabien Forest, MD: Department of Pathology, University Hospital Center (CHU), North Hospital, Saint Etienne, France
Giorgia Leone, MD: Pathology Service, Humanitas Istituto Clinico Catanese, Catania, Italy
Massimo Barberis, MD: Histopathology and Molecular Diagnostics Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCSS) European Institute of Oncology, Milan, Italy
Daoud Rahal, MD: Department of Pathology, Humanitas Clinical and Research Center, Istituto di Ricovero e Cura a Carattere Scientifico (IRCSS), Milan, Italy
Paola Bossi, MD: Department of Pathology, Humanitas Clinical and Research Center, Istituto di Ricovero e Cura a Carattere Scientifico (IRCSS), Milan, Italy
Giovanna Finzi, MD: Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Deborah Marchiori, MD: Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Marco De Luca, MD: Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Fausto Sessa, MD: Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Sergio Harari, MD: Department of Medical Sciences and Community Health, University of Milan, Milan, Italy; Division of Pneumology, San Giuseppe Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCSS) MultiMedica, Milan, Italy
Manuela Spinelli, MD: Cellular Pathology Department, Worcester Royal Hospital, Worcester, United Kingdom
Patrizia Viola, MD: Cellular Pathology Department, Hammersmith Hospital, London, United Kingdom
Paolo Macrì, MD: Division of Oncologic Thoracic Surgery, Humanitas Istituto Clinico Catanese, Catania, Italy
Stefania Maria, MD: Division of Oncologic Thoracic Surgery, Humanitas Istituto Clinico Catanese, Catania, Italy
Antonio Rizzo, MD: Pathology Service, Humanitas Istituto Clinico Catanese, Catania, Italy
Antonio Picone, MD: Department of Oncology, Humanitas Istituto Clinico Catanese, Catania, Italy
Linda Pattini, PhD: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy

Journal volume & issue: Vol. 2, no. 11
p. 100222

Abstract

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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.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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