P40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma

Justin A. Bishop, Julie Teruya-Feldstein, William H. Westra, Giuseppe Pelosi, William D. Travis, Natasha Rekhtman

Research output: Contribution to journalArticle

231 Citations (Scopus)

Abstract

Immunohistochemistry has recently emerged as a powerful ancillary tool for differentiating lung adenocarcinoma and squamous cell carcinoma-a distinction with important therapeutic implications. Although the most frequently recommended squamous marker p63 is extremely sensitive, it suffers from low specificity due to its reactivity in a substantial proportion of lung adenocarcinomas and other tumor types, particularly lymphomas. p40 is a relatively unknown antibody that recognizes ΔNp63a p63 isoform suggested to be highly specific for squamous/basal cells. Here we compared the standard p63 antibody (4A4) and p40 in a series of 470 tumors from the archives of Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Hospital, which included lung squamous cell carcinomas (n=81), adenocarcinomas (n=237), and large cell lymphomas (n=152). The p63 was positive in 100% of squamous cell carcinomas, 31% of adenocarcinomas, and 54% of large cell lymphomas (sensitivity 100%, specificity 60%). In contrast, although p40 was also positive in 100% of squamous cell carcinomas, only 3% of adenocarcinomas, and none of large cell lymphomas had p40 labeling (sensitivity 100%, specificity 98%). The mean percentage of p63 versus p40-immunoreactive cells in squamous cell carcinomas was equivalent (97 vs 96%, respectively, P=0.73). Rare adenocarcinomas with p40 labeling had reactivity in no more than 5% of tumor cells, whereas the mean (range) of p63-positive cells in adenocarcinomas and lymphomas was 26% (1-90%) and 48% (2-100%), respectively. In summary, p40 is equivalent to p63 in sensitivity for squamous cell carcinoma, but it is markedly superior to p63 in specificity, which eliminates a potential pitfall of misinterpreting a p63-positive adenocarcinoma or unsuspected lymphoma as squamous cell carcinoma. These findings strongly support the routine use of p40 in place of p63 for the diagnosis of pulmonary squamous cell carcinoma.

Original languageEnglish (US)
Pages (from-to)405-415
Number of pages11
JournalModern Pathology
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2012

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Squamous Cell Carcinoma
Lymphoma
Lung
Adenocarcinoma
Neoplasms
Sensitivity and Specificity
adjuvant P40
Antibodies
Protein Isoforms
Epithelial Cells
Immunohistochemistry

Keywords

  • adenocarcinoma
  • DNp63
  • p40
  • p63
  • squamous cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Bishop, J. A., Teruya-Feldstein, J., Westra, W. H., Pelosi, G., Travis, W. D., & Rekhtman, N. (2012). P40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Modern Pathology, 25(3), 405-415. https://doi.org/10.1038/modpathol.2011.173

P40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. / Bishop, Justin A.; Teruya-Feldstein, Julie; Westra, William H.; Pelosi, Giuseppe; Travis, William D.; Rekhtman, Natasha.

In: Modern Pathology, Vol. 25, No. 3, 01.03.2012, p. 405-415.

Research output: Contribution to journalArticle

Bishop, JA, Teruya-Feldstein, J, Westra, WH, Pelosi, G, Travis, WD & Rekhtman, N 2012, 'P40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma', Modern Pathology, vol. 25, no. 3, pp. 405-415. https://doi.org/10.1038/modpathol.2011.173
Bishop, Justin A. ; Teruya-Feldstein, Julie ; Westra, William H. ; Pelosi, Giuseppe ; Travis, William D. ; Rekhtman, Natasha. / P40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. In: Modern Pathology. 2012 ; Vol. 25, No. 3. pp. 405-415.
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abstract = "Immunohistochemistry has recently emerged as a powerful ancillary tool for differentiating lung adenocarcinoma and squamous cell carcinoma-a distinction with important therapeutic implications. Although the most frequently recommended squamous marker p63 is extremely sensitive, it suffers from low specificity due to its reactivity in a substantial proportion of lung adenocarcinomas and other tumor types, particularly lymphomas. p40 is a relatively unknown antibody that recognizes ΔNp63a p63 isoform suggested to be highly specific for squamous/basal cells. Here we compared the standard p63 antibody (4A4) and p40 in a series of 470 tumors from the archives of Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Hospital, which included lung squamous cell carcinomas (n=81), adenocarcinomas (n=237), and large cell lymphomas (n=152). The p63 was positive in 100{\%} of squamous cell carcinomas, 31{\%} of adenocarcinomas, and 54{\%} of large cell lymphomas (sensitivity 100{\%}, specificity 60{\%}). In contrast, although p40 was also positive in 100{\%} of squamous cell carcinomas, only 3{\%} of adenocarcinomas, and none of large cell lymphomas had p40 labeling (sensitivity 100{\%}, specificity 98{\%}). The mean percentage of p63 versus p40-immunoreactive cells in squamous cell carcinomas was equivalent (97 vs 96{\%}, respectively, P=0.73). Rare adenocarcinomas with p40 labeling had reactivity in no more than 5{\%} of tumor cells, whereas the mean (range) of p63-positive cells in adenocarcinomas and lymphomas was 26{\%} (1-90{\%}) and 48{\%} (2-100{\%}), respectively. In summary, p40 is equivalent to p63 in sensitivity for squamous cell carcinoma, but it is markedly superior to p63 in specificity, which eliminates a potential pitfall of misinterpreting a p63-positive adenocarcinoma or unsuspected lymphoma as squamous cell carcinoma. These findings strongly support the routine use of p40 in place of p63 for the diagnosis of pulmonary squamous cell carcinoma.",
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