ΔNp63 (p40) distribution inside lung cancer: a driver biomarker approach to tumor characterization

Our plain-English summary of ΔNp63 (p40) distribution inside lung cancer: a driver biomarker approach to tumor characterization, by G. Pelosi, G. Rossi, A. Cavazza, et al (International Journal of Surgical Pathology, 2013).

The study

• Authors: G. Pelosi, G. Rossi, A. Cavazza, L. Righi, P. Maisonneuve, M. Barbareschi, P. Graziano, U. Pastorino, M. Garassino, F. de Braud, M. Papotti
• Journal: International Journal of Surgical Pathology
• Published: 2013;21(3):229-39
• Cited by: 52 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

ΔNp63 (henceforth simply p40) is a squamous/basal-type biomarker corresponding to nontransactivating (non-TA) isoforms of p63 gene. Its prospective relevance as driver biomarker in lung cancer has not yet been thoroughly investigated. In all, 72 adenocarcinomas (ADs), 27 squamous cell carcinomas (SQCs), 13 pleomorphic carcinomas (PLCs), 10 small-cell lung carcinomas (SCLCs), 5 large-cell neuroendocrine carcinomas (LCNECs), 5 adenosquamous carcinomas (ADSQCs), 3 large-cell carcinomas with basaloid features (B-LCC), 2 carcinoids, 2 carcinosarcomas (CS), 2 salivary-gland type tumors (SGTTs) of the lung, and 5 pleural malignant epithelioid mesotheliomas (MEMs) were prospectively diagnosed by morphology and verified by immunohistochemistry for p40, p63, and thyroid transcription factor 1 (TTF1). Histological scores (HS) were devised by multiplying the percentage of immunoreactive cells (0 to 100%) by immunostaining intensity (low = 1 vs strong = 2, according to internal controls). There was a nonrandom distribution of p40 across the diverse tumor groups and cell differentiation lineages, with p40-HS > 100 closely paralleling squamous or myoepithelial carcinomas (SQC, B-LCC, SQC-containing PLC, ADSQC with predominant SQC, SGTT), and p40-HS ≤ 10 pinpointing AD, AD-containing PLC, or CS and neuroendocrine (NE) tumors. At variance, p63-HS was significantly higher than p40 in AD (P < .0001) and NE tumors (P = .0156), with positive predictive value being 83% and 95% and overall accuracy being 95% and 99%, respectively. Also, TTF1 was shared by gland-differentiated and NE tumors. MEM cases were always negative for all biomarkers. The HS-guided assessment of p40 allowed an effective orientation among thoracic malignancies at the level of individual tumor patients thereby contributing to prospectively realize a driver, holistic approach to cancer characterization.

In plain English

This Italian pathology study tested whether staining for the protein p40 (ΔNp63) helps tell lung cancer types apart. It did not examine asbestos exposure. The authors stained 141 consecutively diagnosed lung carcinomas from August and September 2011 for p40, p63 and TTF1, scoring each from 0 to 200. These included 72 adenocarcinomas and 27 squamous cell carcinomas. They also stained 5 pleural malignant epithelioid mesotheliomas for comparison. All 27 squamous cell carcinomas scored above 100 for p40. In contrast, 62 of 72 adenocarcinomas and all neuroendocrine tumors lacked p40 or scored only 1 to 4. p63 was found in 31 of 72 adenocarcinomas. To compare how well the markers separated squamous from non-squamous cell types, the authors used 163 tumor parts, counting mixed tumors' components separately and excluding mesotheliomas. At a cut-off above 100, overall accuracy was 99% for p40 (95% confidence interval 96 to 100%) and 95% for p63 (91 to 98%). The mesotheliomas were negative for all three markers, though one scored 4 for p40 and p63. The authors concluded that p40 should become part of every pathologist's diagnostic toolkit. The article did not state limitations.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective diagnostic pathology (immunohistochemistry) study of consecutively diagnosed tumors
• Who was studied: 141 lung carcinomas consecutively diagnosed at the participating Italian institutions from August 2011 to September 2011: 72 adenocarcinomas, 27 squamous cell carcinomas, 13 pleomorphic carcinomas, 10 small-cell lung carcinomas, 5 large-cell neuroendocrine carcinomas, 5 adenosquamous carcinomas, 3 basaloid large-cell carcinomas, 2 carcinosarcomas, 2 carcinoids and 2 salivary gland-type tumors. Also 5 malignant epithelioid mesotheliomas from Santa Maria Nuova Hospital, used as a control group of non-lung cancers.
• Exposure: No asbestos or other environmental exposure was studied. What was studied was immunohistochemical staining for p40, p63 and TTF1, scored by multiplying the percentage of stained cells by staining intensity.
• Main results:
  • p40 scores were above 100 in all 27 squamous cell carcinomas (range 160 to 200), all 3 basaloid large-cell carcinomas and both salivary gland-type tumors.
  • Several groups either completely lacked p40 or showed p40 scores of at most 1 to 4: 62 of 72 adenocarcinomas, 10 of 13 pleomorphic carcinomas, 2 of 2 carcinosarcomas, and all neuroendocrine tumors.
  • p63, by contrast, was expressed to varying degrees in 31 of 72 adenocarcinomas and 5 of 10 small-cell lung carcinomas.
  • p40 scores were lower than p63 scores in glandular-differentiated carcinomas (P less than .0001) and neuroendocrine-differentiated carcinomas (P = .0156).
  • The differentiation-lineage analyses were based on 163 measures, because separate components of composite tumors were counted separately (38 squamous and 125 non-squamous). Mesotheliomas were excluded from the accuracy analysis.
  • For separating squamous from non-squamous differentiation lineages at a cut-off score above 100, overall accuracy was 99% (95% CI 96-100) for p40 and 95% (95% CI 91-98) for p63.
  • TTF1 was detectable in 65 of 72 adenocarcinomas.
  • Only 4 of 146 thoracic malignancies (2.7%) fell into the intermediate p40 categories (scores 11 to 100).
  • The 5 malignant epithelioid mesotheliomas were negative for p40, p63 and TTF1, except that one tumor had p40 and p63 scores of 4.
• The authors' conclusion: The authors concluded that p40 should become a standard part of every pathologist's diagnostic repertoire. They also concluded that a p40 scoring system sharply separated the two main lung cancer subtypes, adenocarcinoma and squamous cell carcinoma.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Biomarker, Adenocarcinoma, Squamous Cell Carcinoma, Pleomorphic, Carcinoma, Epithelioid, Mesothelioma.

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