Immunohistochemical expression of p63 in pleomorphic adenomas and carcinomas ex-pleomorphic adenomas of salivary glands
Introduction
The p63 protein has been shown to play an essential role in epithelial development and in normal cellular differentiation and may be associated with tumorigenesis in epithelial tissues.1, 2, 3, 4, 5 It is also considered a highly sensitive and specific immunohistochemical marker of myoepithelial cells.3, 4, 6, 7, 8 Recent studies have reported alterations of p63 expression in several human cancers including salivary gland carcinomas.1, 2, 3, 4, 5, 6, 7, 8, 9
Pleomorphic adenomas (PA) are the most frequent benign tumors of the salivary glands. Although monoclonal, PA are composed of epithelial, myoepithelial, and stromal components.10, 11 Malignant transformation of PA have been reported, and it is usually associated with recurrent or longstanding lesions.12, 13, 14 In carcinomas ex-pleomorphic adenomas (Ca ex-PA), malignant transformation is associated with epithelial and/or myoepithelial component resulting in several histological patterns.10, 11, 12, 13, 14, 15 The transformation rarely involves only the myoepithelial component.16 These tumors usually present an aggressive course and a poor clinical prognosis.14, 17, 18
There is no consensus regarding the histological features of PA that are predictive for malignization.19, 20 Moreover, no conclusive finding was observed in several studies of the molecular events associated with this transformation.21, 22, 23, 24, 25
The aim of this study was to assess the p63 immunohistochemical expression in PA and Ca ex-PA in order to better define the possible role of p63 in histogenesis, differentiation and aspects of the transformation from benign to malignant phenotype.
Section snippets
Case selection
Ten cases of PA and 10 cases of Ca ex-PA were retrieved from Department of Pathology, School of Medicine, Federal University of Minas Gerais, the A. C. Camargo Cancer Hospital, and the National Institute of Cancer. The diagnosis of all cases were confirmed by two experienced pathologists (A.H.J.F.M.C. and C.A.R.) and further subtyped according to the World Health Organization (WHO) and Armed Forces Institute of Pathology (AFIP) criteria.10, 11 Accurate Ca ex-PA diagnosis required the presence
Results
The clinical, histopathological and immunohistochemical features of the tumors are summarized in Table 1, Table 2.
The mean age of detection was 39.6 years old (SD ± 11.0) for PA, and 51.7 years old (SD ± 26.9) for Ca ex-PA. Therefore, a difference of 12.1 years was noted between the incidence of these tumors. Female patients were more prevalent in the PA sampling (6:4), while for the Ca ex-PA, the proportion was of 1:1. Parotid was the most affected gland. Histologically, the majority of PA
Discussion
Although PA is the most frequent benign tumor of salivary glands, the Ca ex-PA, its malignant counterpart, is rare. This is due to the fact that time of tumor evolution and the number of recurrences are involved in the mechanisms of malignant transformation of PA into Ca ex-PA as well as being associated with clinical disease progression.12, 13, 14 The recurrences are mostly related to incomplete surgical excision, mainly due to pseudopodia pattern of those tumors.26 Recently, PA have been
Acknowledgements
We thank Heitor Paiva, MD, Lucı́lia Zardo, MD, from National Institute of Cancer (INCA), Rio de Janeiro, Brazil, for providing cases of Ca ex-PA, Lúcia Porto Fonseca de Castro, MD, from School of Medicine of the Federal University of Minas Gerais, Brazil, for her scientific assistance, and Sérgio Cardoso, PhD, from State University of Montes Claros for having critically reviewed the paper.
This work was supported in part by Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG), Conselho
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Myoepithelial carcinoma of the salivary glands: A clinicopathologic study of 29 patients
2015, Journal of Oral and Maxillofacial SurgeryCitation Excerpt :In contrast to the previous study,1 positive immunoreactivity for p63 was noted in 91.7% of our cases (11 of 12). p63 has been reported to be a useful marker of myoepithelial cells in salivary gland neoplasms18; however, it is not a specific marker for myoepithelial cells—squamous cells and their tumors will also be positive.19 Immunoreactivity for SMA was seen in 36% of the cases and was generally weak, which was due to a modification of the smooth muscle phenotype of the tumor cells.
Myoepithelial Tumors: An Update
2015, Surgical Pathology ClinicsCitation Excerpt :EMA is more likely to be positive in ductal cells.1,7–9,16 p63 is positive in 27% to 45% of all benign myoepithelial neoplasms8,22; interestingly, p63 is more uniformly positive in nearly all salivary pleomorphic adenomas.34,35 Frequent expression of PLAG1 (58%–100%) is observed in mixed tumors in soft tissue and skin (Fig. 9), and has been shown to be absent in myoepithelioma.17,18
Tissue microarray is a reliable method for immunohistochemical analysis of pleomorphic adenoma
2014, Oral Surgery, Oral Medicine, Oral Pathology and Oral RadiologyCitation Excerpt :However, because of the frequent loss of TMA cores after immunohistochemical procedures and the high morphologic heterogeneity of pleomorphic adenomas, it would be more advisable to use a second core for each case. In this study, the authors evaluated the immunostaining of CK7 protein, known to be expressed in the luminal cells of ductal structures of normal and neoplastic tissues23; CD34, which has been shown to adequately illustrate the vascular component of PA24; the nuclear marker p63, which is related to myoepithelial differentiation25; and the proliferative marker Ki67, which indicates the proliferative potential of the tumor.20 In conclusion, despite the finding that one well-sampled 2.0-mm core could provide results similar to those of TMAs arranged in duplicate and triplicate, the authors suggest that, because of the possibility of tissue loss during additional laboratory procedures, 2.0-mm TMAs assembled in duplicate are a more desirable arrangement, representing a reliable, cost-effective, and high-throughput method for immunohistochemical study of PA.
Comparison of Ki-67, cyclin E, and p63 in benign and malignant human pleomorphic adenoma
2012, Oral Surgery, Oral Medicine, Oral Pathology and Oral RadiologyThe role of the VEGF-C/-D/flt-4 autocrine loop in the pathogenesis of salivary neoplasms
2012, Pathology Research and PracticeCitation Excerpt :In our cases of pleomorphic adenoma, given the fact that the cells we examined morphologically resembled myoepithelial cells, p63 and SMA staining was comparatively evaluated. The noted coexpression of p63 and SMA confirmed the expected myoepithelial differentiation [3,7]. Furthermore, after serial sections examination, the staining was expressed in the same area as the VEGF-C, VEGF-D and flt-4 expression.
Expression of hMLH1 and hMSH2 proteins in pleomorphic adenoma of minor salivary glands: Relationship with clinical and histologic findings
2009, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and EndodontologyCitation Excerpt :Therefore, histologic evidence of hyalinization was scored and described as follows: normal (no hyalinization), mild (faint tinge of hyalinization), moderate (strongly marked but focalized), or severe (wide hyalinization). In addition, based on the literature,5,12-15 the cases were stratified as low- and high-risk subtypes for their estimated potential for malignant transformation. High-risk subtypes included those lesions characterized by the presence of either 1 clinical and 1 histologic criterion, or 2 histologic criteria (Table I).