Differential expression of p63 isotypes (DeltaN and TA) in salivary gland neoplasms: biological and diagnostic implications.
To determine the association between the expression of p63 gene isoforms (TA and DeltaN) and salivary gland tumorigenesis, we performed reverse transcription-polymerase chain reaction analysis of these markers in 71 benign and malignant salivary gland neoplasms. The results were correlated with the expression of Notch ligand JAG1 gene and the clinicopathologic features and the full-length p63 protein expression by immunohistochemistry. Both p63 isoforms were either negative or weakly expressed in normal salivary gland tissues. TAp63 was highly expressed in most benign tumors and was either negative or weakly positive in most carcinomas. Conversely, DeltaNp63 was negative or faintly positive in most benign neoplasms and was highly expressed in adenoid cystic, mucoepidermoid, and myoepithelial carcinomas. Immunohistochemical analysis using anti-full-length p63 protein showed ubiquitous nuclear staining in basal and myoepithelial cells in both benign and malignant neoplasms. JAG1 was expressed in most benign and malignant tumors and did not correlate with p63 isoforms expression. We conclude that (1) p63 isoforms are differentially expressed in most benign and malignant tumors and may play distinct biological roles in certain salivary gland neoplasms; (2) p63 immunostaining do not correlate with the isoforms expression; and (3) isoform-specific antibodies are required for better cellular localization and biological correlations.
Maruya
Shin-Ichiro
S
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Kies
Merrill S
MS
Williams
Michelle
M
Myers
Jeffery N
JN
Weber
Randal S
RS
Batsakis
John G
JG
El-Naggar
Adel K
AK
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000235:Adenolymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008949:Adenoma, Pleomorphic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology; D000072099:Serrate-Jagged Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000072099:Serrate-Jagged Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins