p63 is a p53-homologous
nuclear protein that appears to play a crucial role in regulation of stem cell commitment in squamous and other epithelia. In this study, p63 expression was examined in benign lung and in
neoplasms of pulmonary origin. Eighty sections from routinely fixed and processed archival bronchoscopic biopsy or lobectomy specimens were pretreated with
citric acid (pH 6.0) for
antigen retrieval, then incubated overnight with anti-p63
monoclonal antibody 4A4. Slides were stained using a
streptavidin-
biotin kit and diaminobenzidine as chromagen, and were counterstained with
hematoxylin. In normal lung, p63 intensely stained nuclei of bronchial reserve cells but did not
stain ciliated cells, alveolar epithelial cells, or nonepithelial cells. The lower strata of squamous metaplastic bronchial epithelium stained positively. All
squamous-cell carcinomas stained positively (
n = 30). In some well-differentiated
carcinomas, staining was found at the periphery of
tumor nests but was negative in central zones showing squamous maturation. Poorly differentiated
carcinomas showed very high proportions (80% to 100%) of p63-positive nuclei. All
small-cell carcinomas were p63 negative (n = 9). Staining of
bronchioloalveolar carcinomas (n = 7) and
adenocarcinomas (n = 23) was variable: some
tumors showed no detectable staining, others showed heterogeneously positive staining.
Adenosquamous carcinomas (n = 5) displayed a unique basalar staining pattern.
Carcinoid tumors were almost entirely negative (n = 5). We conclude that p63 is expressed in benign bronchial stem cells, in neoplastic cells with either squamous differentiation or squamous differentiating potential, and in a subpopulation of
adenocarcinomas. p63 immunostaining may also aid in some histopathologic distinctions, such as in small biopsies where the differential diagnosis is poorly differentiated
squamous carcinoma versus
small-cell carcinoma. A stem cell biology-based classification system for
squamous carcinomas is proposed.