Elsevier

Oral Oncology

Volume 42, Issue 2, February 2006, Pages 154-160
Oral Oncology

Immunohistochemical expression of p63 in pleomorphic adenomas and carcinomas ex-pleomorphic adenomas of salivary glands

https://doi.org/10.1016/j.oraloncology.2005.06.026Get rights and content

Summary

Alteration of the p63 protein expression has been associated with several human cancers including salivary gland tumors. We sought to assess the p63 expression in pleomorphic adenomas (PA) and carcinoma ex-pleomorphic adenomas (Ca ex-PA), since this protein has been related to myoepithelial phenotype and the biological behavior of cancer. Ten samples of PA and ten of Ca ex-PA were submitted to immunohistochemistry using a monoclonal anti-p63 antibody, clone 4A4. p63 was regularly expressed in myoepithelial cells’ nuclei of the normal glandular parenchyma and in PA, but it was completely absent in five out of the ten samples of Ca ex-PA. (P < 0.05 by Fisher’s exact test). Apparently, only those cases depicting some myoepithelial differentiation were positive. Our data suggest that loss of myoepithelial differentiation is important in the evolution of Ca ex-PA, and corroborate the hypothesis that p63 antigen may be a useful marker of myoepithelial cells in salivary glands neoplasms.

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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