p63 expression in assessment of bronchioloalveolar proliferations of the lung

Abstract

Discrimination of well-differentiated pulmonary adenocarcinoma from reactive bronchioloalveolar epithelium can be difficult on routine histology, especially with small biopsies. Ancillary studies to help in this distinction are desirable. p63, a p53-homologous nuclear protein, is a marker of reserve cells of the bronchus and terminal lobular unit. In this study, 33 cases of adenocarcinoma (20 open lung and 13 transbronchial/percutaneous biopsies) and 43 cases of benign lungs with fibrosis and metaplasia (22 open lung and 21 transbronchial/ percutaneous biopsies) were studied for nuclear p63 expression by immunohistochemistry (Dako, Carpinteria, CA, USA). Five additional cases each of atypical adenomatous hyperplasia and adenosquamous carcinoma and three cases of squamous carcinoma (all open lung biopsies) were also stained. The diagnostic categories of benign lung conditions were usual interstitial pneumonia, parenchymal scar, cryptogenic organizing pneumonia and diffuse alveolar damage. In neoplastic cases, p63 positivity was calculated as percentage of all tumor cells examined. In areas of normal lung, p63 decorated the reserve cells of large and small airways and occasional cells of the distal lobular unit. In fibrotic reactive processes, an interrupted but distinct pattern of nuclear staining was present in all cases, with staining of basal cells of the airways as well as bronchiolar-and squamous-metaplastic epithelium (43/43, 100%). p63 immunoreactivity was less uniform in areas of acute lung injury within these cases. One adenocarcinoma and two cases of atypical adenomatous hyperplasia showed strong immunoreactivity (480%), while three adenocarcinomas highlighted only rare tumor nuclei (o5% of tumor cells). Morphologic areas where p63 immunostaining was not helpful included the junction of normal lung and lepidic growth of adenocarcinoma, and retrograde spread of adenocarcinoma into small airways. Our results highlight the differential expression of p63 across various bronchioloalveolar lesions. Moreover, p63 may be helpful in distinguishing reactive from neoplastic glandular proliferations in the lung.

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

“…This finding indicates that, although uncommon, p63 expression can occur in these tumors, but when present, the percentage of positive cells is usually lower than that seen in squamous carcinomas. It should also be mentioned that p63 has also been reported in 12-33% of the lung adenocarcinomas, 43,45,49 a finding which indicates that p63 immunostaining has no utility in distinguishing these tumors from mesotheliomas.…”

Lung development: orchestrating the generation and regeneration of a complex organ

“…BSCs also line this region of the airway tract in humans but their presence has not been well documented in rodent lungs (Chilosi et al, 2002;Sheikh et al, 2004). There is evidence that, in the bronchiolar region, a subpopulation of secretory cells that express Scgb1a1 but lack expression of Cyp2f2 can act as facultative progenitor cells.…”

Basal cells of the human airways acquire mesenchymal traits in idiopathic pulmonary fibrosis and in culture

“…18 Upon damage in airway epithelium, the basal cells show increased reactivity demonstrated by increased expression of p63, a basal cell restricted transcription factor and its downstream target cytokeratin 14 (CK14). 19,20 Recent studies have implicated p63 with EMT. Das et al 21 showed that fibrotic lesions in oral submucosa showed marked upregulation of p63 and Oh et al 22 showed that primary human keratinocytes transfected with ΔNp63 underwent EMT when they had depleted their normal proliferative capacity.…”