p63 Expression in Salivary Gland Tumors: Role ofΔNp73L in Neoplastic Transformation

Abstract

To illustrate the role of p63 and its truncated variants in salivary gland tumors, 23 consecutive tumors and 6 normal salivary glands were studied immunohistochemically with anti-p63 antibody and by reverse transcriptase (RT) and nested polymerase chain reaction (PCR) to detect p63 isoform expression. Normal salivary glands: p63 antibody-stained basal and myoepithelial cells; by RT and nested PCR, the 2 main isoforms were present, whereas ΔNp73L was absent. Tumors: p63 antibody was positive in the following: Warthin tumor (WT) (3/3), oncocytoma (OC) (1/1), pleomorphic adenoma (PA) (7/7), polymorphous-low-grade adenocarcinoma (PLGA) (3/3), adenoid-cystic carcinoma (ADCC)(3/4), epithelial-myoepithelial-cell carcinoma (EMC) (1/1), and myoepithelial-cell carcinoma (MCC) (1/1). By RT and nested PCR all tumors expressed p63 irrespective of their morphologic differentiation. The ΔNp73L isoform was present in tumoral tissue but absent in normal salivary gland. These data suggest that p63, particularly its splice variant ΔNp73L, is involved in the neoplastic transformation of salivary glands.

Keywords

p63 ΔNp73L salivary gland tumor splice variant myoepithelium basal cell

Get full access to this article

View all access options for this article.

References

Brunner HG , Hamel BC , Bokhoven HV . P63 gene mutations and human developmental syndromes. Am J Hum Genet 112:284-290 2002

Mills AA , Zheng B , Wang X , Vogel H , Roop DR , Bradley A . P63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398:708-713 1999

Yang A , Kaghad M , Wang Y , Gillett E , Fleming MD , Dotsch V , Andrews NC , Caput D , McKeon F . p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant negative activities. Mol Cell 2:305-316, 1998

Yang A , Schweitzer R , Sun D , Kaghad M , Walker N , Bronson RT , Tabin C , Sharpe A , Caput D , Crum C , McKeon F . p63 is essential for regenerative proliferation in limb, craniofacial, and epithelial development. Nature 398:714-718, 1999

Nylander K , Coates PJ , Hall PA . Characterization of the expression pattern of p63 alpha and deltaNp63 alpha in benign and malignant oral epithelial lesions. Int J Cancer 87:372, 2004

Senoo M , Tsuchiya Y , Matsumara Y , Mori T , Saito Y , Kato H , Okamoto T , Habu S . Transcriptional dysregulation of the p73L/p63/p51/p40/KET gene in human squamous cell carcinomas: Expression of deltaNp73L, a novel dominant negative isoform, and loss of expression of the potential tumor suppressor gene p51. Br J Cancer 84:1235-1241, 2001

Foschini MP , Gaiba A , Cocchi R , Pennesi MG , Gatto MR , Frezza GP , Pession A . Pattern of p63 expression in squamous cell carcinoma of the oral cavity. Virchows Arch 444:332-339 2004

Weber A , Langhanki L , Schutz A , Gerstner A , Bootz F , Wittekind C , Tannapfel A . Expression profiles of p53, p63, and p73 in benign salivary gland tumors. Virchows Arch 441:428-436 2002

Cheuk W , Chan JKC , Ngan RKC . Dedifferentiation in adenoid cystic carcinoma of salivary gland. An uncommon complication associated with an accelerated clinical course. Am J Surg Pathol 23:465-472 1999

10.

Magrini E , Pragliola A , Farnedi A , Betts CM , Cocchi R , Foschini MP . Cytogenetic analysis of myoepithelial cell carcinoma of salivary gland. Virchows Arch 444:82-86 2004

11.

Burstein D , Chandaneep N , Wang BY , Unger Pl . Immunohistochemical detection of p53 homolog p63 in solid cell nests, papillary thyroid carcinoma, and Hashimoto’s thyroiditis: A stem cell hypothesis of papillary carcinoma oncogenesis. Hum Pathol 35:465-473 2004

12.

Chilosi M , Zamo’ A , Brighenti A , Malpelli G , Montagna L , Piccoli P , Pedron S , Lestani M , Inghirami G , Scarpa A , Dogliosi C , Minestrina F . Constitutive expression of deltaNp63alpha isoform in human thymus and thymic epithelial tumors. Virchows Arch 443:171-183 2003

13.

Di Como JC , Urist MJ , Babayan I , Drobnyak M , Hedvat CV , Teruya-Feldstein J , Pohar K , Hoos A , Cordona-Cardo C . p63 expression profiles in human normal and tumoral tissues. Clin Canc Res 8:494-501, 2002

14.

Reis-Filho JS , Simpson PT , Martins A , Preto AN , Gartner R , Schmitt F . Distribution of p63, cytokeratins 5/6, and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP multitumor tissue microarray. Virchows Arch 443:122-132 2003

15.

Bilal H , Handra-Luca A , Bertrand JC , Fouret PJ . p63 is expressed in basal and myoepithelial cells of human normal and tumor salivary gland tissues. J Histochem Cytochem 51:133-139, 2003

16.

Ihrler S , Zietz C , Sendelhofert A , Lang S , Blasenbreu-Vogt S , Lohrs U . A morphogenetic concept of salivary duct regeneration and metaplasia. Virchows Arch 440:519-526 2002

17.

Nagao T , Gaffey TA , Serizawa H , Sugano I , Ishida Y , Yamazaki K , Tokashiki R , Yoshida T , Minato H , Kay PA , Lewis JE . Dedifferentiated adenoid cystic carcinoma: A clinicopathologic study of 6 cases. Mod Pathol 16:1265-1272 2003