J Pathol Transl Med.  2018 Sep;52(5):283-289. 10.4132/jptm.2018.08.14.

p40 Immunohistochemistry Is an Excellent Marker in Primary Lung Squamous Cell Carcinoma

  • 1Department of Pathology, Universiti Kebangsaan Malaysia Medical Centre, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. reenarahayu@ppukm.ukm.edu.my


Lung cancer is the third most common cancer worldwide. With major advances in the molecular testing of lung cancers and the introduction of targeted therapies, the distinction between adenocarcinoma and squamous cell carcinoma as well as pathologic subtyping has become important. Recent studies showed that p40 is highly specific for squamous and basal cells and is superior to p63 for diagnosing lung squamous cell carcinoma. The aim of this study was to evaluate the use of p40 immunohistochemical stain in the diagnosis of non-small cell lung carcinoma and its potential to replace current p63 antibody as the best immunohistochemical squamous marker.
Seventy formalin-fixed paraffin-embedded cases previously diagnosed as primary lung squamous cell carcinoma (n = 35) and lung adenocarcinoma (n = 35) from January 2008 to December 2016 were retrieved. The results of tumour cell immunoreactivity for p40 and p63 antibodies in lung squamous cell carcinoma and lung adenocarcinoma were compared.
p40 was expressed in 27 cases of lung squamous cell carcinoma (77.1%). All cases of lung adenocarcinoma (35/35, 100%) were negative for p40. p63 expression was positive in 30 cases of lung squamous cell carcinoma (85.7%) and 13 cases of lung adenocarcinoma (37.1%). Reactivity for both p40 and p63 in lung squamous cell carcinoma was strong and diffuse, whereas variable reactivity was observed in lung adenocarcinoma.
p40 is an excellent marker for distinguishing lung squamous cell carcinoma from adenocarcinoma, and p40 expression is equivalent to p63 expression in lung squamous cell carcinoma.


Non-small cell lung carcinoma; Immunohistochemistry; Lung neoplasms; p40; p63

MeSH Terms

Carcinoma, Squamous Cell*
Epithelial Cells*
Lung Neoplasms


  • Fig. 1. Intensity score for positive p40 and p63 nuclear staining in tumour cells. (A) Score 1+ for weak positivity. (B) Score 2+ for moderate positivity. (C) Score 3+ for strong positivity.

  • Fig. 2. Analysis of p40 and p63 expression in lung squamous cell carcinoma and adenocarcinoma. (A) Intensity score. (B) Tumour cell immunoreactivity.

  • Fig. 3. Poorly differentiated tumour with squamous-like morphology. Tumour cells with abundant eosinophilic cytoplasm and distinct cell borders (A), intercellular bridges (B), and keratinization features (C).


1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136:E359–86.
2. Azizah AM, Nor Saleha IT, Noor Hashimah A, Asmah ZA, Mastulu W. Malaysian National Cancer Registry report 2007-2011. Malaysia cancer statistics, data and figure. Putrajaya: National Cancer Institute, Ministry of Health;2016.
3. Travis WD, Brambilla E, Noguchi M, et al. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med. 2013; 137:668–84.
4. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. WHO classification of tumours of the lung, pleura, thymus and heart. 4th ed. Lyon: International Agency for Research on Cancer;2015.
5. Kadota K, Nitadori J, Rekhtman N, Jones DR, Adusumilli PS, Travis WD. Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis. Am J Surg Pathol. 2015; 39:1170–80.
6. Pelosi G, Fabbri A, Bianchi F, et al. DeltaNp63 (p40) and thyroid transcription factor-1 immunoreactivity on small biopsies or cellblocks for typing non-small cell lung cancer: a novel two-hit, sparing-material approach. J Thorac Oncol. 2012; 7:281–90.
7. Rekhtman N, Ang DC, Sima CS, Travis WD, Moreira AL. Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens. Mod Pathol. 2011; 24:1348–59.
8. Nobre AR, Albergaria A, Schmitt F. p40: a p63 isoform useful for lung cancer diagnosis: a review of the physiological and pathological role of p63. Acta Cytol. 2013; 57:1–8.
9. Bishop JA, Teruya-Feldstein J, Westra WH, Pelosi G, Travis WD, Rekhtman N. p40 (DeltaNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Mod Pathol. 2012; 25:405–15.
10. Nonaka D. A study of ΔNp63 expression in lung non-small cell carcinomas. Am J Surg Pathol. 2012; 36:895–9.
11. Mukhopadhyay S, Katzenstein AL. Subclassification of non-small cell lung carcinomas lacking morphologic differentiation on biopsy specimens: Utility of an immunohistochemical panel containing TTF-1, napsin A, p63, and CK5/6. Am J Surg Pathol. 2011; 35:15–25.
12. Tacha D, Bremer R, Haas T, Qi W. An immunohistochemical analysis of a newly developed, mouse monoclonal p40 (BC28) antibody in lung, bladder, skin, breast, prostate, and head and neck cancers. Arch Pathol Lab Med. 2014; 138:1358–64.
13. Perez-Moreno P, Brambilla E, Thomas R, Soria JC. Squamous cell carcinoma of the lung: molecular subtypes and therapeutic opportunities. Clin Cancer Res. 2012; 18:2443–51.
14. Nicholson AG, Gonzalez D, Shah P, et al. Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFR mutation analysis. J Thorac Oncol. 2010; 5:436–41.
15. Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol. 2013; 8:823–59.
16. Rekhtman N, Paik PK, Arcila ME, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res. 2012; 18:1167–76.
17. Travis WD, Rekhtman N, Riley GJ, et al. Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift. J Thorac Oncol. 2010; 5:411–4.
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