p63 In pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors

Wang, Beverly Y.; Gil, Joan; Kaufman, David; Gan, Li; Kohtz, D. Stave; Burstein, David

doi:10.1053/hupa.2002.126878

Cited by 163 publications

(181 citation statements)

References 22 publications

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“…p63 plays a role in stem cell commitment in squamous epithelium. 37 Some reported that p63 was expressed in pulmonary squamous cell carcinoma but not in small cell carcinomas, 37,38 whereas others reported that large cell neuroendocrine carcinoma and small cell carcinoma had p63 expression. 39,40 The reported differences of frequency of p63 expression in small cell carcinoma may be due to different identification methods for positive cells.…”

Section: Discussionmentioning

confidence: 99%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

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The distinction between pulmonary large cell neuroendocrine carcinoma and small cell carcinoma is difficult in some cases. Some propose that these carcinomas should be classified as one high-grade neuroendocrine carcinoma. We examined biological features of small cell carcinoma (n ¼ 23), large cell neuroendocrine carcinoma (n ¼ 17), and classic large cell carcinoma (n ¼ 12). The average ratio of nuclear diameter of the tumor cells to that of lymphocytes for small cell carcinoma was smaller than that for large cell neuroendocrine carcinoma (Po0.0001). The frequencies of the expressions of CD56, mASH1, TTF-1, and p16 were higher and that of NeuroD was lower in small cell carcinoma than in large cell neuroendocrine carcinoma. The frequency of loss of heterozygosity at 3p was higher in high-grade neuroendocrine carcinomas than in classic large cell carcinoma (P ¼ 0.0002). Allelic losses at D5S422 (5q33) were more frequent in small cell carcinoma than in large cell neuroendocrine carcinoma (P ¼ 0.0091). Mean fractional regional loss indices of the tumors were 0.38, 0.65, and 0.72 for patients with classic large cell carcinoma, large cell neuroendocrine carcinoma, and small cell carcinoma, respectively (P ¼ 0.0003). Five-year overall survivals of patients with classic large cell carcinoma, large cell neuroendocrine carcinoma and small cell carcinoma in stage I were 67, 73, 60%, respectively. Patients with NeuroD expression had better survivals, and those with p63 expression had poorer survivals in large cell neuroendocrine carcinoma. Patients with TTF-1 expression had poorer survivals in small cell carcinoma. Our data suggest that large cell neuroendocrine carcinoma and small cell carcinoma are different morphologically, phenotypically, and genetically, although there are some overlapping features. Although further studies are needed to analyze the biological behavior of high-grade neuroendocrine carcinomas including sensitivity to chemotherapy, the pathological distinction of large cell neuroendocrine carcinoma from small cell carcinoma may be necessary to treat the patients with neuroendocrine tumors.

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Section: Discussionmentioning

confidence: 99%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

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“…21 In the nonneoplastic lung, p63 is normally expressed by bronchial reserve cells, and lower strata of metaplastic squamous epithelia, and it may play a role in stem cell commitment in squamous epithelium. 22 The high molecular weight keratin antibody recognizes cytokeratins 1, 5, 10, and 14 in the Moll catalog 23 and reacts with airway basal cells and metaplastic squamous cells. Morphologic small cell carcinomas showing the typical immunohistochemical profile (TTF-1 þ /p16 þ /p63À), except for reactivity of some cells with high molecular weight keratin, should be carefully scrutinized for populations of large neoplastic cells.…”

Section: Discussionmentioning

confidence: 99%

Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach

et al. 2005

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Accurate morphologic distinction between small cell carcinoma and poorly differentiated squamous cell carcinoma has critical therapeutic significance, but can be limited by crush artifact, tumor necrosis, limited tumor representation, and overlapping morphologic features. We evaluated a panel of antibodies for their efficacy in distinguishing between these neoplasms. Formalin-fixed paraffin-embedded tissue sections of small cell carcinomas and poorly differentiated squamous cell carcinomas underwent immunohistochemical staining with antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A). Of 28 small cell carcinomas, 26 (93%) small cell carcinomas showed diffuse moderate or strong staining for thyroid transcription factor-1 with no staining for high molecular weight keratin and p63. In contrast, 27/28 (96%) poorly differentiated squamous cell carcinomas manifested opposite immunoreactivities, with diffuse moderate or strong staining for high molecular weight keratin and p63, and no or minimal staining for thyroid transcription factor-1. In two additional cases originally interpreted as small cell carcinoma, high molecular weight keratin highlighted small numbers of neoplastic large cells, leading to reclassification as combined small cell and nonsmall cell carcinomas. p16(INK4A) expression varied widely in poorly differentiated squamous cell carcinomas, but was consistently moderate or strong and diffuse in small cell carcinomas, and proved helpful in the two thyroid transcription factor-1-negative small cell carcinomas. This study demonstrates that a panel consisting of antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A) is highly effective for distinguishing between small cell carcinoma and poorly differentiated squamous cell carcinoma. This panel also facilitates diagnosis of combined small cell and non-small cell carcinomas.

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“…[7][8][9] In the lung, it has been mainly studied in different histologic subtypes of epithelial neoplasms, with the highest expression consistently noted in squamous cell carcinomas. 10,11 The pattern of staining in squamous carcinomas is also unique, with outer 'basilar' cells showing greater nuclear immunoreactivity compared to inner differentiated 'terminal' cells. 11 The frequency of expression in pulmonary adenocarcinomas is lower, with most cases showing only focal staining.…”

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confidence: 99%

“…10,11 The pattern of staining in squamous carcinomas is also unique, with outer 'basilar' cells showing greater nuclear immunoreactivity compared to inner differentiated 'terminal' cells. 11 The frequency of expression in pulmonary adenocarcinomas is lower, with most cases showing only focal staining. Neuroendocrine carcinomas are nonimmunoreactive for the most part, with the exception of some large-cell carcinomas.…”

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confidence: 99%

“…Interestingly, adenosquamous carcinomas are almost always positive, with immunoreactivity confined to squamoid areas, with one study describing staining of basilar cells in the glandular component as well. 11 While p63 expression in normal lung has been described, its expression in benign lung processes with reactive epithelial hyperplasia and metaplasia has not been examined. With the success of p63 as a basal cell marker in the prostrate, and the presence of p63-immunoreactive basal cells in the proximal portion of the normal bronchioloalveolar tree, we compared expression of this nuclear protein in pulmonary adenocarcinomas, atypical adenomatous hyperplasia and a variety of acute, subacute and chronic reactive lung conditions, in order to assess the usefulness of this stain in the differential diagnosis of glandular proliferations encountered in open lung biopsies and in smaller diagnostically challenging transbronchial/percutaneous lung biopsies.…”

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p63 expression in assessment of bronchioloalveolar proliferations of the lung

et al. 2004

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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.

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p63 In pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors

Cited by 163 publications

References 22 publications

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach

p63 expression in assessment of bronchioloalveolar proliferations of the lung

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