Aberrant Localization of  -Catenin Correlates with Overexpression of Its Target Gene in Human Papillary Thyroid Cancer

Ishigaki, Katsu

doi:10.1210/jc.87.7.3433

Cited by 52 publications

(44 citation statements)

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“…31,32,39,[59][60][61][62][63][64] An alteration in the gene encoding cyclin D1 has not been reported in thyroid neoplasia, but a link between aberrant b-catenin expression and upregulation of cyclin D1 has been shown in a variety of neoplasms. [65][66][67] In this study, the nuclear expression of cyclin D1 was markedly increased in the vast majority of indolent and aggressive neoplasms. This finding contrasts with conventional papillary thyroid carcinomas in which cyclin D1 is only expressed in a low percentage of neoplastic cells.…”

Section: Discussionmentioning

confidence: 49%

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

et al. 2011

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The majority of papillary thyroid carcinoma is indolent and associated with long-term survival. The columnar cell variant, however, is a rare subtype that is variable in biological behavior; some are clinically aggressive, whereas others are more clinically indolent. Tumor size, tumor circumscription, and encapsulation may influence the behavior of columnar cell carcinomas. Other variables including genetic changes and putative biomarkers associated with malignant growth have not been thoroughly examined in these neoplasms. In this study, nine cases of columnar cell variant of papillary thyroid carcinoma from three institutions were classified as clinically indolent or aggressive based on pathological features, clinical history, and outcome. Indolent tumors were typically small, circumscribed or encapsulated, and from younger female patients, whereas aggressive tumors were large, locally aggressive, associated with regional and distant metastasis, and from older male patients. The missense mutation, V600E in the BRAF oncogene (BRAF V600E ), was detected in three of nine of cases, of which two were clinically aggressive. Immunohistochemical evaluation of neoplasiaassociated markers showed increased nuclear cyclin D1 expression, elevated Ki-67 proliferation indices, and predominantly weak nuclear p53 staining in both indolent and aggressive tumors. Expression of b-catenin was largely restricted to a membranous pattern in both tumor types. Cytoplasmic expression of bcl-2 was overall mildly reduced in indolent neoplasms. Nuclear expression of estrogen and progesterone receptors was increased in both indolent and aggressive neoplasms, but was without sex-or age-related differences; however, whereas progesterone receptor expression was diffuse and strong in clinically indolent carcinomas, its expression was diminished in aggressive neoplasms. Recognition of the clinicopathological characteristics and the molecular and immunophenotypic features of the columnar cell variant of papillary thyroid carcinoma may aid in characterizing neoplasms that behave indolently or aggressively. Keywords: BRAF (BRAF V600E ); b-catenin; columnar cell variant; cyclin D1; papillary thyroid carcinoma Papillary thyroid carcinoma is a common endocrine neoplasm that is typically indolent and associated with long-term survival. This favorable biological behavior reflects the vast majority of conventional and histological variants of well-differentiated papillary thyroid carcinoma. However, a more aggressive tumoral growth characterizes a small subset that behaves more akin to poorly differentiated and undifferentiated thyroid carcinoma. Initially included in this group of aggressive neoplasms, the columnar cell variant is a rare subtype with variable biological behavior. Early reports described tumors with fast growth rates, aggressive local invasion, high rates of recurrence, early metastasis to regional lymph nodes and distant

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Section: Discussionmentioning

confidence: 49%

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

et al. 2011

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“…Our data are in partial agreement with the aberrant expression and localization of b-catenin that has been reported in a variety of human cancers including colon, 36 liver, 37 stomach, 38 pancreas, 39 bone, 40 and thyroid. 41 Reports that have studied the expression of b-catenin in human lung cancer remain controversial. Some authors, in agreement with the present observations, reported restricted cytoplasmic localization and never found b-catenin nuclear translocation, 34,[42][43][44][45] whereas some other studies show cytoplasmic and nuclear localization of b-catenin.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Blanco

Vicent

Elizegi

et al. 2004

Laboratory Investigation

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Loss of the epithelial phenotype and disruption of adhesion molecules is a hallmark in the epithelialmesenchymal transition (EMT) reported in several types of cancer. Most of the studies about the relevance of adhesion and junction molecules in lung cancer have been performed using established tumors or in vitro models. The sequential molecular events leading to EMT during lung cancer progression are still not well understood. We have used a rat model for multistep lung carcinogenesis to study the status of adherens and tight junction proteins and mesenchymal markers during EMT. After silica-induced chronic inflammation, rats sequentially develop epithelial hyperplasia, preneoplastic lesions, and tumors such as adenocarcinomas and squamous cell carcinomas. In comparison with normal and hyperplastic bronchiolar epithelium and with hyperplastic alveolar type II cells, the expression levels of E-cadherin, a-catenin and b-catenin were significantly reduced in adenomatoid preneoplastic lesions and in late tumors. The loss of E-cadherin in tumors was associated with its promoter hypermethylation. a-and b-catenin dysregulation lead to cytoplasmic accumulation in some carcinomas. No nuclear b-catenin localization was found at any stage of any preneoplastic or neoplastic lesion. Zonula occludens protein-1 was markedly decreased in 66% of adenocarcinomas and in 100% squamous cell carcinomas. The mesenchymal-associated proteins N-cadherin and vimentin were analyzed as markers for EMT. N-cadherin was de novo expressed in 32% of adenocarcinomas and 33% of squamous cell carcinomas. Vimentin-positive tumor cells were found in 35% of adenocarcinomas and 88% of squamous cell carcinomas. Mesenchymal markers were absent in precursor lesions, both hyperplastic and adenomatoid. The present results show that silica-induced rat lung carcinogenesis is a good model to study EMT in vivo, and also provide in vivo evidence suggesting that the changes in cell-cell adhesion molecules are an early event in lung carcinogenesis, while EMT occurs at a later stage.

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“…Such mutations disrupt phosphorylation sites of -catenin and lead to protein stabilization. Mutations and abnormal nuclear localization of -catenin have been observed, along with overexpression of its target genes c-Myc and cyclin D1, in thyroid malignancies (Ishigaki et al, 2002). Although increased levels of cytoplasmic -catenin are observed in most thyroid cancer cells, mutations of -catenin that lead to nuclear localization of the protein are limited to PDTC and ATC suggesting a role in tumor progression (Garcia-Rostan et al, 2001).…”

Section: Genetic Alterations In Anaplastic Thyroid Carcinomasmentioning

confidence: 99%

Molecular Biology of Thyroid Cancer

Viglietto¹,

Marco²

2011

Contemporary Aspects of Endocrinology

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Aberrant Localization of -Catenin Correlates with Overexpression of Its Target Gene in Human Papillary Thyroid Cancer

Cited by 52 publications

References 0 publications

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Molecular Biology of Thyroid Cancer

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