P63 expression in papillary and anaplastic carcinomas of the thyroid gland: lack of an oncogenetic role in tumorigenesis and progression.
P53 is considered one of the most important tumor suppressor genes and is mutated in up to 50% of all neoplasms. Well-differentiated thyroid carcinomas (WDTCs) only infrequently harbor p53 mutations. In contrast, these genetic alterations have been described in approximately 85% of anaplastic thyroid carcinomas and are considered a fundamental event in the malignant progression of WDTCs. However, alternative mechanisms to overcome p53 tumor suppressing properties in WDTCs and anaplastic carcinomas (ACs) have not been clarified to date. p63, a p53-homologue, has been recently characterized. In contrast to p53, p63 gene encodes six isoforms, three with transactivating and three with dominant negative (deltaN-p63) activities on p53 reporter genes. We hypothesized that overexpression of deltaN-p63 isoforms might constitute an alternative mechanism to overcome p53 tumor suppressing properties in WDTCs and ACs lacking p53 alterations. We semiquantitatively evaluated p53 and p63 immunoexpression in 12 papillary carcinomas (PC) and 11 anaplastic carcinomas. Only nuclear expression was considered specific. All PCs lacked p53 expression; at variance, nine ACs showed p53 immunoreactivity (+: 1 case; ++: 6 cases; +++: 2 cases). In PCs, p63 expression was restricted to scattered neoplastic cells juxtaposed to the basement membrane of papillary projections and to foci of squamous metaplasia. In ACs, p63 expression was observed in three cases, one of which lacked concurrent p53 immunoexpression. Our results do not support the hypothesis that p63 might constitute an alternative mechanism to overcome p53 tumor suppressing properties in thyroid neoplasms.
Preto
Ana
A
Institute of Molecular Pathology and Immunology, University of Porto, Portugal.
Reis-Filho
Jorge S
JS
Ricardo
Sara
S
Soares
Paula
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010750:Phosphoproteins / Q000096:biosynthesis*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins