Significance of p53-binding protein 1 (53BP1) expression in thyroid papillary microcarcinoma: association with BRAFV600E mutation status.

AIMS: In a previous report, we proposed that analysis of 53BP1 expression by immunofluorescence could be a useful tool in estimating the level of genomic instability (GIN), as well as the malignant potential, of thyroid tumours. In an attempt to clarify the value of 53BP1 expression as a new molecular marker for the aggressiveness of thyroid papillary microcarcinoma (PMC), we assessed the association between the type of 53BP1 expression and clinicopathological features such as tumour size, extrathyroidal invasion, lymph node metastasis and BRAF(V) (600E) mutation of PMC. METHODS AND RESULTS: A total of 36 surgically resected thyroid tumours, including 13 PMC and 23 conventional papillary thyroid carcinomas (PTC), were available for this study. Analysis using immunofluorescence revealed that the incidence of an abnormal or high DNA damage response (DDR) type of 53BP1 expression was significantly higher in PTC than PMC. BRAF(V) (600E) mutation was not associated significantly with tumour aggressiveness in either PMC or PTC cases. Abnormal/high DDR type of 53BP1 expression was associated closely with both BRAF(V) (600E) mutation and papillary and/or trabecular architecture of PMC. CONCLUSIONS: Abnormal/high DDR type of 53BP1 expression might be associated with GIN and papillary/trabecular morphology at an early stage of PTC carcinogenesis through BRAF(V) (600E) mutation.

Radiation-associated small cell neuroendocrine carcinoma of the thyroid: a case report with molecular analyses.

BACKGROUND: Neuroendocrine tumor (NET) of the thyroid other than medullary carcinoma is extremely rare. We describe here a case of calcitonin-negative small cell neuroendocrine carcinoma (SCNEC), which occurred in a thyroid gland that had previously been irradiated at high dose (60 Gy) for pharyngeal cancer, with molecular analyses for follicular cell origin. PATIENT FINDINGS: The tumor cells were small with fine chromatin, inconspicuous nucleoli, and inapparent cytoplasm, and showed neuroendocrine architectures such as palisading, rosettes, and trabeculae. Mitotic figures were numerous exceeding 10 mitoses per 10 high-power fields. The tumor cells invaded into several vessels and metastasized to regional lymph nodes. Immunohistochemically, the tumor cells were strongly positive for neuroendocrine markers and thyroglobulin (Tg), a marker of thyroid follicular cells but negative for calcitonin and carcinoembryonic antigen (CEA). Expression of Tg and thyrotropin receptor (TSHR) were confirmed by quantitative real-time polymerase chain reaction (RT-PCR). Ki-67 labeling index was more than 70% in the tumor cells. Taken together, the tumor was diagnosed as SCNEC of the thyroid. Genetic analyses also revealed microsatellite abnormalities of the phosphatase and tensin homolog (PTEN) gene, suggesting that functional loss of PTEN contributes to carcinogenesis. CONCLUSIONS: This is the first report describing a SCNEC of the thyroid with molecular analyses that provide evidence for a follicular epithelial origin.