P73 expression in basal layers of head and neck squamous epithelium: a role in differentiation and carcinogenesis in concert with p53 and p63?
P73, a p53-homologue gene, has been studied for its possible role in head and neck squamous epithelium (HNSE) differentiation and carcinogenesis. P73 RNA and protein were analysed in 50 biopsies, including well- and moderately-differentiated carcinomas, and 21 matched normal adjacent tissues. P73 immunohistochemical analyses revealed intense p73 nuclear staining in basal and parabasal cells of normal squamous epithelium, in contrast with complete absence of staining in the more superficial cell layers. Moderately-differentiated carcinomas demonstrated homogeneous and diffuse staining in all tumour cells, while only basal cells were stained in well-differentiated carcinomas as in normal tissue. No correlation was observed between p73 and p53 protein expression. Immunostaining for p63, another p53-related protein previously described as being involved in HNSE morphogenesis and overexpressed in head and neck squamous cell carcinomas (HNSCC), was found to be similar to p73 labelling in carcinomas, but spread to the more differentiated layers in normal epithelium. Biallelic expression of p73 was found in tumours as well as in matched normal tissues. Comparison of p73 transcript levels between tumours and normal tissues showed decreased mRNA expression in 5/17 (30%) tumours independently of the differentiation status. Mutation and loss of heterozygosity analyses of the p73 gene revealed wild type status and no deletion. Our results strongly suggest that: (i) p73 is associated with homeostasis and control of differentiation of head and neck squamous epithelium probably in concert with p53 and p63; (ii) down-regulation of p73 expression could participate in HNSE carcinogenesis.
Faridoni-Laurens
L
L
Unité des Marqueurs Génétiques des Cancers, Département de Biologie Clinique, Institut Gustave Roussy, 94805 Villejuif, France.
Bosq
J
J
Janot
F
F
Vayssade
M
M
Le Bihan
M L
ML
Kaghad
M
M
Caput
D
D
Bénard
J
J
Ahomadegbe
J C
JC
D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000378:metabolism; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008565:Membrane Proteins; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins