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TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majo...

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Autores principales: Cabibi, Daniela, Bellavia, Sandro, Giannone, Antonino Giulio, Barraco, Nadia, Cipolla, Calogero, Martorana, Anna, Rodolico, Vito, Cajozzo, Massimo, Florena, Ada Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169837/
https://www.ncbi.nlm.nih.gov/pubmed/31935792
http://dx.doi.org/10.3390/diagnostics10010025
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author Cabibi, Daniela
Bellavia, Sandro
Giannone, Antonino Giulio
Barraco, Nadia
Cipolla, Calogero
Martorana, Anna
Rodolico, Vito
Cajozzo, Massimo
Florena, Ada Maria
author_facet Cabibi, Daniela
Bellavia, Sandro
Giannone, Antonino Giulio
Barraco, Nadia
Cipolla, Calogero
Martorana, Anna
Rodolico, Vito
Cajozzo, Massimo
Florena, Ada Maria
author_sort Cabibi, Daniela
collection PubMed
description TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (ΔNp63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as “TTF-1+ p63+ adenocarcinoma”. The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as “adenocarcinoma, solid variant”, in keeping with the presence of TTF-1 expression and p40 negativity. A “wild type” genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these “basal-type tumors” like those in the better known “basal-like” cancer of the breast.
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spelling pubmed-71698372020-04-22 TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit Cabibi, Daniela Bellavia, Sandro Giannone, Antonino Giulio Barraco, Nadia Cipolla, Calogero Martorana, Anna Rodolico, Vito Cajozzo, Massimo Florena, Ada Maria Diagnostics (Basel) Article TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (ΔNp63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as “TTF-1+ p63+ adenocarcinoma”. The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as “adenocarcinoma, solid variant”, in keeping with the presence of TTF-1 expression and p40 negativity. A “wild type” genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these “basal-type tumors” like those in the better known “basal-like” cancer of the breast. MDPI 2020-01-06 /pmc/articles/PMC7169837/ /pubmed/31935792 http://dx.doi.org/10.3390/diagnostics10010025 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cabibi, Daniela
Bellavia, Sandro
Giannone, Antonino Giulio
Barraco, Nadia
Cipolla, Calogero
Martorana, Anna
Rodolico, Vito
Cajozzo, Massimo
Florena, Ada Maria
TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit
title TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit
title_full TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit
title_fullStr TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit
title_full_unstemmed TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit
title_short TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit
title_sort ttf-1/p63-positive poorly differentiated nsclc: a histogenetic hypothesis from the basal reserve cell of the terminal respiratory unit
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169837/
https://www.ncbi.nlm.nih.gov/pubmed/31935792
http://dx.doi.org/10.3390/diagnostics10010025
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