p63 immunoreactivity in lung cancer: yet another player in the development of squamous cell carcinomas?

Pelosi, Giuseppe; Pasini, Felice; Stenholm, Catharina Olsen; Pastorino, Ugo; Maisonneuve, Patrick; Sonzogni, Angelica; Maffini, Fausto; Pruneri, Giancarlo; Fraggetta, Filippo; Cavallon, Alessandra; Roz, Elena; Iannucci, Antonio; Bresaola, Enrica; Viale, Giuseppe

doi:10.1002/path.1166

Cited by 130 publications

(156 citation statements)

References 44 publications

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“…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. Zhang et al 38 reported that they defined the tumor as p63-negative if less than 10% of tumor cells were stained.…”

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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“…Therefore, it is conceivable that activation (or induction) of p63 may divert the intraductal neoplastic cells towards a more mature, metaplastic process. As in other organs, 3,9,[23][24][25] DNp63 is a reliable marker of squamous differentiation also in pancreatic carcinoma. Among invasive carcinomas of the pancreas, DNp63 immuno-expression is largely limited to the areas of squamous differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…As the key molecule of the epithelial stratification program, 13 DNp63 expression is highly specific for squamous differentiation in neoplasia, and is usually not detected in nonsquamous carcinomas such as adenocarcinoma, small cell carcinoma or mesothelioma and others. 3,9,21,[23][24][25][26] This is valuable in the differential diagnosis of poorly differentiated malignant tumors of undetermined origin.…”

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confidence: 99%

DeltaNp63 expression in pancreas and pancreatic neoplasia

et al. 2005

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DeltaNp63 (DNp63) has become widely used, in particular, for distinguishing invasive carcinomas from noninvasive ducts by highlighting the myoepithelial or basal cells in the breast and prostate, respectively. It is not known whether this marker may have any application in another exocrine organ, the pancreas. As the ductal and intraductal proliferations of this organ become better characterized, the need for markers to distinguish among these processes increases. We investigated immunohistochemical expression of DNP63 in 105 cases. A total of 25 cases were non-neoplastic pancreata, 25 were pancreatic intraepithelial neoplasia (PanIN) of various grades, and 50 were examples of pancreatic ductal adenocarcinoma. Sections of non-neoplastic pancreata included various types of non-neoplastic processes such as squamous/transitional metaplasia (five cases), which can be mistaken for high-grade PanINs, as well as various degrees of reactive ductal atypia and incidental microcysts with attenuated lining (five cases). No DNp63 expression was noted in normal pancreatic ducts. On the other hand, all five foci of squamous/transitional metaplasia were strongly and uniformly positive for this marker. DNp63 labeling was also noted in those incidental microcysts lined by attenuated cells, seen amidst normal pancreatic lobules. All PanINs were negative. Among invasive carcinomas, DNp63 expression was detected only in areas of squamous differentiation and was completely absent in ordinary ductal areas. Based on this observation, five additional cases of adenosquamous/squamous carcinoma was retrieved and stained, and the squamous components of all of these were also positive. In conclusion, (I) DNp63 is a reliable marker of squamous differentiation in the pancreas. It is valuable in distinguishing squamous/transitional metaplasia from PanINs, a distinction of importance for both researchers and diagnosticians. Among invasive carcinomas, it seems to be entirely specific for areas of squamous differentiation. (II) Those incidental microcysts seen in acinar lobules and lined by attenuated cells are also positive for DNp63, which suggests that they may be metaplastic in nature, and that they do not represent neoplastic cells. (III) Unlike the ducts of other exocrine organs, breast and prostate, there are no DNp63-expressing cells in the normal pancreatic ducts, and therefore, this marker cannot be used in distinguishing invasive carcinomas from the non-invasive ducts. (IV) No p63-expressing 'stem' cells are present in the pancreas.

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“…34,35 In each tumor, the sarcomatoid and epithelial components were assessed separately, recording the percentage of neoplastic cells immunoreactive for the different antigens in either components.…”

Section: Immunohistochemistrymentioning

confidence: 99%

K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung

et al. 2004

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We investigated 27 pleomorphic carcinomas of the lung for exon 1 K-ras gene mutations using polymerase chain reaction-single-strand conformation polymophism analysis and direct sequencing. All pleomorphic carcinomas were biphasic, that is, composed of an adeno-, squamous-or large-cell-carcinomatous component associated with a spindle-and/or giant-cell component. Of 27 cases, six (22%) showed K-ras codon 12 mutations, which is a figure higher than that previously reported on in pure sarcoma-like pleomorphic carcinomas. Five tumors displayed the same mutation in both the epithelial and the sarcomatoid components, whereas in one tumor the mutation was restricted to the epithelial component. All mutations occurred in smokers, and were transversions, including GGT (glycine) to TGT (cysteine) change in two cases, to GCT (alanine) in two and to GTT (valine) in two. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clinicopathological variable, suggesting that K-ras mutations are early events in the development of these tumors. Our results indicate that most, though not all, biphasic pleomorphic carcinomas of the lung are monoclonal in origin, and that cigarette smoking may have a causative role in the development of K-ras alterations in these tumors, as all mutations are transversions.

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p63 immunoreactivity in lung cancer: yet another player in the development of squamous cell carcinomas?

Cited by 130 publications

References 44 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

DeltaNp63 expression in pancreas and pancreatic neoplasia

K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung

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