2004 Fiscal Year Final Research Report Summary
Molecular and Pathological Study on Prognostic Factors of Papillary Thyroid Carcinoma
| Project/Area Number |
13670175
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
HIROKAWA Mitsuyoshi The University of Tokushima, Department of Pathology, Associated Professor, 大学院・ヘルスバイオサイエンス研究部, 助教授 (80173277)
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| 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)
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| Project Period (FY) |
2001 – 2004
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| Keywords | Thyroid / Papillary carcinoma / Colonic polyposis / APC gene / Cribriform type / Morula / beta-catenin |
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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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