Download Abstracts about p40 (ΔNp63)

Abstracts about p40 (∆Np63)
1. Mod Pathol. 2012 Mar;25(3):405-15. doi: 10.1038/modpathol.2011.173. Epub 2011 Nov 4
p40 (∆Np63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma.
Bishop JA, Teruya-Feldstein J, Westra WH, Pelosi G, Travis WD, Rekhtman N.
Department of Surgical Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
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 ∆Np63-a 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% (190%) 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.
2. J Thorac Oncol. 2012 Feb;7(2):281-90.
∆Np63 (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.
Pelosi G, Fabbri A, Bianchi F, Maisonneuve P, Rossi G, Barbareschi M, Graziano P,
Cavazza A, Rekhtman N, Pastorino U, Scanagatta P, Papotti M.
Department of Pathology and Laboratory Medicine,Fondazione IRCCS National Cancer Institute, Milan, Italy.
[email protected]
INTRODUCTION: Diagnosing non-small cell lung cancer on biopsy/cellblock samples by morphology
may be demanding. As sparing material for molecular testing is mandatory, a minimalist
immunohistochemistry (IHC)-based diagnostic approach is warranted by means of novel, reliable, and
easy-to-assess biomarkers.
METHODS: Forty-six consecutive biopsy/cellblock samples and the corresponding resection
specimens (as the gold standard for morphology and IHC) from 30 adenocarcinomas (AD), 10
squamous carcinomas (SQC), 5 adenosquamous carcinomas (ADSQC), and 1 sarcomatoid
carcinoma (SC) were IHC-evaluated for p40 [corresponding to nontransactivating ∆Np63 isoforms]
and thyroid transcription factor-1 (TTF1) by semiquantitative assessment. For p40, also
immunodecoration intensity was taken into account and dichotomized as strong or low.
RESULTS: Nonrandom and overlapping distributions of the relevant markers were found in
biopsy/cellblock and surgical specimens, which closely correlated with each other and the diverse
tumor categories, with no differences in area under curve-receiver-operating-characteristic curves for
each marker between any two samples, including p40 and p63. Diagnostic combinations were p40/TTF1+ or TTF1- for AD (where p40 was negative, apart from 5/30 AD showing at the best 1-2%
tumor cells with low intensity); p40+/TTF1- (p40 strong and by far higher than 50%) for SQC; and
p40+/TTF1+ or p40+/TTF1- (p40 strong and less than 50%) for ADSQC. The single SC case was
p40-/TTF1-, suggesting glandular lineage. Practically, 41/46 (89%) tumors were correctly classified by
IHC on small samples, including 30 AD, 10 SQC, 1/5 ADSQC, and no SC. Underdiagnosis of
ADSQC was actually because of sampling error of biopsies/cellblocks rather than insufficient
biomarker robustness, whereas underdiagnosis of SC was really because of the failure of either
marker to highlight epithelial-mesenchymal transition.
CONCLUSIONS: This minimalist IHC-based model of p40 and TTF1 on biopsy/cellblock samples
was effective to correctly subtype most cases of lung cancer.
3. Am J Surg Pathol. 2012 Feb 24. [Epub ahead of print]
A Study of ∆Np63 Expression in Lung Non-Small Cell Carcinomas.
Nonaka D.
*Department of Histopathology, The Christie Hospital †School of Cancer and Enabling Sciences, University of Manchester
School of Medicine, Manchester, UK.
Distinguishing between lung adenocarcinoma and squamous cell carcinoma is becoming increasingly
important, given the different treatment regimens available. Although histologic subdivision between
the two is generally not difficult in differentiated tumors, it can be challenging in poorly differentiated
tumors and may require a panel of immunohistochemistry stains. The p63 gene encodes two different
N-termini (TA and ∆N). ∆Np63 is selectively expressed in squamous cell carcinoma, whereas TAp63
is not restricted only to it. 4A4, a widely used anti-p63 antibody, identifies both isoforms and is
expressed in about 15% of adenocarcinomas, and, although generally focal, its expression can be
diffuse.
In this study, a total of 150 lung adenocarcinomas and 50 squamous cell carcinomas were
immunostained by antibodies for p63 (4A4), ∆Np63 (p40), and TTF-1 (8G7G3/1). Twenty-seven
adenocarcinomas (18%) were positive for p63 to a variable extent, with diffuse reaction being seen in
13 tumors (8.7%). p63 expression was seen in all subtypes of adenocarcinomas, except for the
mucinous type. p40 was negative in all adenocarcinomas. All squamous cell carcinomas were
diffusely positive for both p63 and p40. Four of 27 p63-positive adenocarcinomas were negative for
TTF-1. p63 expression is not uncommonly seen in adenocarcinomas, whereas ∆Np63 (p40)
expression is specific for squamous cell carcinoma, with sensitivity comparable to that of p63
expression. Presence of p63-positive cells in poorly differentiated lung adenocarcinoma may be
erroneously interpreted as evidence of squamous cell differentiation.
p40 appears to be a more reliable marker for squamous cell carcinoma.
4. Appl Immunohistochem Mol Morphol 12:240-247, 2004
p63 expression in lung carcinoma: a tissue microarray study of 408 cases.
Au NH, Gown AM, Cheang M, Huntsman D, Yorida E, Elliott WM, Flint J, English J,
Gilks CB, Grimes HL.
Genetic Pathology Evaluation Centre, Department of Pathology and Prostate Research Centre, Vancouver General
Hospital, the British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
p63 is a recently discovered member of the p53 family that has been shown to be important in the
development of epithelial tissues. p63 may also play a role in squamous cell carcinomas of the lung,
head and neck, and cervix, and its expression is increased in these tumors. The purpose of this study
was to investigate the expression of p63 in a broad spectrum of histologic types of lung tumors. A
total of 441 cases of primary lung tumors with follow-up data were identified, and the paraffinembedded tissue blocks were used to construct a duplicate core tissue microarray. After review of the
tissue cores, 408 cases, consisting of 123 squamous cell carcinomas, 93 adenocarcinomas, 68 large
cell carcinomas, 68 classic carcinoids, 31 atypical carcinoids, 11 large cell neuroendocrine
carcinomas, and 14 small cell carcinomas, were adequate for analysis. Immunohistochemistry was
performed at 2 different laboratories using monoclonal antibody 4A4 to detect the expression of p63,
using different staining protocols.
p53 expression was also studied with immunohistochemistry using monoclonal antibody DO-7.
Kaplan-Meier curves were plotted to compare the survival of p63-expressing versus nonexpressing
tumors. A large proportion of squamous cell carcinomas expressed p63 (96.9%), most showing strong
positive nuclear immunoreactivity. Expression in other nonsmall cell lung cancers was also present.
Thirty percent of adenocarcinomas and 37% of large cell carcinomas showed p63 expression. In the
neuroendocrine tumors, an increasing proportion of tumors stained for p63 as tumor grade increased;
1.9% of classic carcinoids, 30.8% of atypical carcinoids, 50% of large cell neuroendocrine
carcinomas, and 76.9% of small cell carcinomas were positive. Approximately half of the positively
staining neuroendocrine cases showed strong staining.
Expression of p63 was of prognostic significance in neuroendocrine tumors (P < 0.0001), with highergrade tumors more likely to express p63. Correlation between p63 and p53 expression was not
observed (P = 0.18) in non small-cell lung cancer; however, a significant correlation between the 2
markers was found in neuroendocrine tumors (P < 0.0001). p63 staining was repeated with a
different staining protocol, yielding similar results overall but a lower percentage of positive cases
(34.2% vs. 48.4% of tumors positive). In conclusion, p63 expression is consistently expressed in
squamous cell carcinoma in the lung, but is also expressed in a subset of adenocarcinomas and large
cell carcinomas. Pulmonary neuroendocrine tumors also show p63 staining in some instances,
particularly in higher-grade tumors, and the majority of small cell carcinomas are p63-positive. These
results suggest that p63 may be involved in oncogenesis in a broader range of tumors than was
previously thought.