A Study of ΔNp63 (p40) Expression in Non-Small Cell Lung Carcinomas
Daisuke Nonaka. The Christie Hospital, University of Manchester, Manchester, United Kingdom
Background: A majority of lung carcinomas constitute three major subtypes; small cell carcinoma, adenocarcinoma and squamous cell carcinoma (SCC). Distinguishing between the latter two is becoming important because different treatment regimen is available. While histological subdivision between the two is not generally difficult in differentiated tumors, it can be challenging in poorly differentiated tumors, and may require a panel of immunohistochemistry stains, e.g., p63 and CK5/6 for squamous marker and TTF-1 and Napsin A for adenocarcinoma marker. The typical immunoprofile is TTF-1 + or - /p63- for adenocarcinoma and TTF1 -/p63 + for SCC. p63 gene encodes two different N-termini (TA and ΔN). ΔNp63 is selectively expressed in basal and squamous cells, and is expressed in SCC whereas TAp63 is not restricted only to SCC. 4A4, the most widely used anti-p63 antibody, identifies both isoforms, and is expressed in about 15% of adenocarcinomas, and though generally focal, its expression can be more than focal in a subset of adenocarcinomas. This study investigates the utility of ΔNp63 to distinguish between pulmonary adenocarcinomas and SCC.
Design: A total of 150 primary lung adenocarcinomas (3 BAC/in situ, 35 acinar, 2 papillary, 40 solid, 58 mixed, and 12 mucinous) and 35 SCC were retrieved, and immunostains were performed by using tissue microarrays for p63 (4A4), ΔNp63 (p40), and TTF-1. The extent of staining was graded as 1+, 1-25%; 2+, 25-50%; 3+, 50-75%; 4+, >75%.
Results: 26 adenocarcinomas (17%) contained p63-positive neoplastic cells to a variable extent with diffuse (3+/4+) reaction being seen in 12 tumors (8%). p63 expression was seen in all of the subtypes of adenocarcinomas except for mucinous type. p40 was negative in all adenocarcinomas. All SCC were positive for both p63 and p40 predominantly in diffuse fashion. 116 adenocarcinomas (77%) were positive for TTF-1 to variable extent while all SCC were negative. p63 expression was seen in 23 TTF-1 positive adenocarcinomas (20%) while p40 was completely negative in all of the TTF-1 positive tumors.
Conclusions: p63 is not uncommonly seen in adenocarcinomas while p40 is specific in SCC and as sensitive as p63. Presence of p63-positive cells in poorly differentiated lung adenocarcinoma may be erroneously interpreted as evidence of squamous cell differentiation. p40 can potentially be a more reliable marker for SCC.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 294, Tuesday Morning