Beta-catenin dysregulation in thyroid neoplasms: down-regulation, aberrant nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumor phenotypes and poor prognosis.
Am J Pathol
; 158(3): 987-96, 2001 Mar.
Article
em En
| MEDLINE
| ID: mdl-11238046
ABSTRACT
beta-catenin has a role in cell adhesion and Wnt signaling. It is mutated or otherwise dysregulated in a variety of human cancers. In this study we assess beta-catenin alteration in 145 thyroid tumors samples from 127 patients. beta-catenin was localized using immunofluorescence and mutational analysis was performed by single-strand conformational polymorphism. Membrane beta-catenin expression was decreased in eight of 12 (66%) adenomas and in all 115 carcinomas (P < 0.0001). Among carcinomas, reduced membrane beta-catenin was associated with progressive loss of tumor differentiation (P < 0.0001). CTNNB1 exon 3 mutations and nuclear beta-catenin localization were restricted to poorly differentiated [7 of 28 (25%) and 6 of 28 cases (21.4%), respectively] or undifferentiated carcinomas [19 of 29 (65.5%) and 14 of 29 (48.3%) cases, respectively]. Poorly differentiated tumors always featured mutations involving Ser and Thr residues and were characterized by Thr to Ile amino acid substitutions (P = 0.0283). The association between CTNNB1 exon 3 mutations and aberrant nuclear immunoreactivity (P = 0.0020) is consistent with Wnt activation because of stabilizing beta-catenin mutations. Low membrane beta-catenin expression as well as its nuclear localization or CTNNB1 exon 3 mutations are significantly associated with poor prognosis, independent of conventional prognostic indicators for thyroid cancer but not of tumor differentiation. Analysis of beta-catenin dysregulation may be useful to objectively subtype thyroid neoplasms and more accurately predict outcomes.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Glândula Tireoide
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Carcinoma
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Biomarcadores Tumorais
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Adenoma
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Transativadores
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Proteínas do Citoesqueleto
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Pathol
Ano de publicação:
2001
Tipo de documento:
Article