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. The Johns Hopkins Medical Institutions, Baltimore, MD; Memorial Sloan-Kettering Cancer Center, New York, NY; Fondazione IRCCS National Cancer Institute and University of Milan School of Medicine, Milan, Italy
Background: Immunohistochemistry has recently emerged as a powerful ancillary tool for differentiating lung adenocarcinoma and squamous cell carcinoma – a distinction with important therapeutic implications. While 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 ΔNp63 – a p63 isoform suggested to be highly specific for squamous/basal cells.
Design: The standard p63 antibody (4A4) and p40 were compared 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).
Results: p63 was positive in 100% of squamous cell carcinomas, 31% of adenocarcinomas and 54% of large cell lymphomas (sensitivity 100%, specificity 60%). In contrast, while 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.
Conclusions: In summary, p40 is equivalent to p63 in sensitivity for squamous cell carcinoma, but it is markedly superior to p63 in specificity. In effect, any more than minimal (5%) p40 reactivity is entirely specific for the squamous phenotype, eliminating 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.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 295, Tuesday Morning