| Co-Investigator(Kenkyū-buntansha) |
SANO Toshiaki The University of Tokushima, Department of Pathology, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (80154128)
HORIGUCHI Hidehisa The University of Tokushima, Department of Pathology, Assistant, 大学院・ヘルスバイオサイエンス研究部, 助手 (40304505)
若槻 真吾 徳島大学, 医学部, 助手 (70294668)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
The cribriform-morular variant (C-MV), an unusual and peculiar subtype of papillary thyroid carcinoma (PTC), has been observed frequently in familial adenomatous polyposis (FAP)-associated thyroid carcinoma and also in sporadic thyroid carcinoma. We performed a pathological and molecular genetic study of 5 cases of cribriform-morular variant of papillary thyroid carcinoma. Grossly, one FAP-associated tumour and one sporadic tumour were multicentric and the others were solitary. Histologically, the tumours were encapsulated and exhibited a combination of cribriform, follicular, trabecular, solid, and papillary patterns of growth, with morular areas. Immunohistochemically, the tumour cells showed cytoplasmic expression of thyroglobulin, neuron-specific enolase, epithelial membrane antigen, high- and low-molecular-weight cytokeratins, vimentin, and bcl-2 protein ; nuclear expression of oestrogen and progesterone receptors, and retinoblastoma protein ; and cytoplasmic and nuclear accumulat
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ion of beta-catenin. Germline APC mutation was identified in only one FAP patients. Somatic mutation analysis of exon 3 of the beta-catenin gene revealed alterations in seven tumors from all five individuals. Our data suggested that accumulation of mutant beta-catenin contributes to the development of cribriform-morular variant of papillary thyroid carcinoma. Additionally, we compared the morules in cribriform-morular variant of papillary thyroid carcinoma with squamous metaplasia in diffuse sclerosing variant of papillary thyroid carcinoma. The squamous metaplastic cells were immunopositive for low- and high-molecular-weight cytokeratin, whereas the morular cells were negative or focally positive. The morular cells showed weak cytoplasmic positivity for beta-catenin, and the cell membrane was not highlighted. Some nuclei of the morular cells were also positive for this antibody. Beta-catenin was intensively positive along the cell membrane of the metaplastic cells, and did not react against the nuclei or cytoplasm. Bcl-2 was positive in the morular cells, but negative in the metaplastic cells. We argue that morules appear in connection with nuclear and cytoplasmic aberrant localization of beta-catenin, and are not an early form of squamous metaplasia. Less
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