Pattern of p63 expression in squamous cell carcinoma of the oral cavity

Foschini, Maria Pia; Gaiba, Alessia; Cocchi, R; Pennesi, Maria G.; Gatto, Maria Rosaria; Frezza, G.P.; Pession, Annalisa

doi:10.1007/s00428-003-0969-x

Cited by 50 publications

(56 citation statements)

References 17 publications

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“…Such discrepancies might be due to the monoclonal A4A antibody used in immunohistochemical analyses. Foschini et al have been suggested that A4A antibody recognizes all of p63 isoforms (TAp63, ΔNp63) that may have different functions (56). Therefore, this antibody was not able to discriminate between the different isoforms.…”

Section: Discussionmentioning

confidence: 99%

Increased ΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma

et al. 2011

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Abstract. This study examined immunohistochemical expression of ΔNp63, a keratinocyte stem cell marker, in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) and then to elucidate usefulness of ΔNp63 as a marker for diagnosis and prognosis. One-hundred and twelve cases of OL and 81 cases of OSCC were analyzed by immunohistochemical staining for ΔNp63, Ki-67, and cytokeratin 14. These labeling indices (LIs) were calculated, and the association of these LIs with clinicopathologic characteristics in the OL and OSCC was evaluated. In the OL, these LIs increased significantly according to the severity of epithelial dysplasia (p<0.0001). ΔNp63-LI in the OL with malignant transformation was significantly higher than that in the OL without (49.3 vs. 34.2%; p<0.01). In the OSCC, the LIs increased significantly in association with the histologic grade (p<0.0001). A significant difference between the high and low ΔNp63-LI groups was found in the incidence of cervical lymph node and distant metastasis (p<0.05). The prognosis of the high ΔNp63-LI (mean value >73.8%) group is poorer than that of the low ΔNp63-LI (mean value ≤73.8%) group (p<0.05). These results suggested that increased ΔNp63 expression is involved in malignant transformation in epithelial dysplasia and poor prognosis in OSCC. Introductionp63 gene is a homolog of p53, it is located on chromosome 3q27-29 and encodes multiple isotypes with divergent abilities in a variety of organs (1-4). p63 has two different promoter domains that generate two protein isoforms, TAp63 and ΔNp63; each isoform yields three isotypes (α, β, γ) generated by alternative splicing of the p63 COOH terminus; and TAp63 includes an NH 2 -terminal transactivation domain, which is absent in ΔNp63 (1-4,6,7). TAp63 transactivates p53 target genes to induce apoptosis by inhibiting cell proliferation in response to exposure of cells to DNA-damaging agents such as ultraviolet irradiation. In contrast, ΔNp63 exerts dominant-negative activities against TAp63 and p53, and ΔNp63 is thus considered as an oncoprotein (1,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).Recent studies have shown that p63 is essential for craniofacial development during morphogenesis, because p63 -/-mice represented craniofacial abnormalities including hypoplasia of jaws and defects of the teeth, hair follicles, lachrymal glands, and salivary glands (1,15). Furthermore, p63 -/-mice showed lack of squamous stratification in the epidermis and oral epithelium, suggesting that p63 plays critical roles in the epithelial development. Pellegrini et al also demonstrated that p63 was expressed in keratinocyte stem cells and involved in the proliferation and maintenance of this cell population (16). Thus, p63 has been characterized as a marker of keratinocyte stem cells.In the tumorigenesis as well as morphogenesis, the existence of a stem-like cell population with a self-renewal potential, capacity of development into multiple lineages, extensive proliferation activity, and high migration capability in the tumor tissue was revealed. ...

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Section: Discussionmentioning

confidence: 99%

Increased ΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma

et al. 2011

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“…Eight different protein isoforms of p63 based on alternative splicing have been described. 9,10 The aim of the present study was to further evaluate in a large case series the immunohistochemical detection of p63 as a prognostic marker especially in low-stage (stage I-II) patients of Merkel cell carcinoma. Moreover, in all cases p63 expression by immunohistochemistry and molecular analysis of its variants were studied in parallel, to compare the two different procedures.…”

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confidence: 99%

Expression of p63 is the sole independent marker of aggressiveness in localised (stage I–II) Merkel cell carcinomas

et al. 2011

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Merkel cell carcinoma of the skin is a malignant neuroendocrine tumour, whose prognostic criteria are a matter of dispute. Specifically, no predictor is presently available in stage I-II tumours. We collected clinical and follow-up data from 70 Merkel cell carcinomas of the skin. The same cases were studied for p63 expression by immunohistochemistry, by reverse-transcription PCR (RT-PCR) and TP63 gene status by FISH and for presence of Merkel cell polyomavirus by PCR. Stage emerged as a significant prognostic parameter (P ¼ 0.008). p63 expression, detected in 61% (43/70) of cases by immunohistochemistry, was associated with both decreased overall survival (Po0.0001) and disease-free survival (Po0.0001). Variable expression patterns of the different p63 isoforms were found only in cases immunoreactive for p63. In these latter lesions, at least one of the N-terminal p63 isoforms was detected and TAp63a was the most frequently expressed isoform. TP63 gene amplification was observed by FISH in only one case. Presence of Merkel cell polyomavirus DNA sequences was detected in 86% (60/70) of Merkel cell carcinomas and did not emerge as a significant prognostic parameter. Merkel cell carcinoma cases at low stage (stage I-II) represented over half (40/70 cases, 57%) of cases, and the clinical course was uneventful in 25 of 40 cases while 15 cases died of tumour (10/40 cases) within 34 months or were alive with disease (5/40 cases) within 20 months. Interestingly, a very strict correlation was found between evolution and p63 expression (Po0.0001). The present data indicate that p63 expression is associated with a worse prognosis in patients with Merkel cell carcinoma, and in localised tumours it represents the single independent predictor of clinical evolution.

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“…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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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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Pattern of p63 expression in squamous cell carcinoma of the oral cavity

Cited by 50 publications

References 17 publications

Increased ΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma

Increased ΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma

Expression of p63 is the sole independent marker of aggressiveness in localised (stage I–II) Merkel cell carcinomas

DeltaNp63 expression in pancreas and pancreatic neoplasia

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