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


Authors: Bishop, J. A.; Teruya-Feldstein, J.; Westra, W. H.; Pelosi, G.; Travis, W. D.; Rekhtman, N.
Article Title: P40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma
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. © 2012 USCAP, Inc. All rights reserved.
Keywords: controlled study; human tissue; unclassified drug; squamous cell carcinoma; cancer diagnosis; sensitivity and specificity; adenocarcinoma; lung adenocarcinoma; lung carcinoma; protein p63; large cell lymphoma; isoprotein; immunocompetent cell; p63; protein antibody; protein p40; antibody labeling; dnp63; p40; protein p40 antibody; protein p63 antibody 4a4
Journal Title: Modern Pathology
Volume: 25
Issue: 3
ISSN: 0893-3952
Publisher: Nature Research  
Date Published: 2012-03-01
Start Page: 405
End Page: 415
Language: English
DOI: 10.1038/modpathol.2011.173
PROVIDER: scopus
PUBMED: 22056955
DOI/URL:
Notes: --- - "Export Date: 2 April 2012" - "CODEN: MODPE" - "Source: Scopus"
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  1. Natasha Rekhtman
    424 Rekhtman
  2. Julie T Feldstein
    297 Feldstein
  3. William D Travis
    743 Travis