TY - JOUR
T1 - Expansion of microsatellite in the thyroid hormone receptor-alpha1 gene linked to increased receptor expression and less aggressive thyroid cancer.
AU - Onda, Masamitsu
AU - Li, Daisy
AU - Suzuki, Shinichi
AU - Nakamura, Izumi
AU - Takenoshita, Seiichi
AU - Brogren, Carl-Henrik
AU - Stampanoni, Sabina
AU - Rampino, Nicholas
N1 - Keywords: Adenocarcinoma, Follicular; Carcinoma, Papillary; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Microsatellite Repeats; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Receptors, Thyroid Hormone; Thyroid Neoplasms; Tumor Cells, Cultured
PY - 2002
Y1 - 2002
N2 - PURPOSE: The purpose of this study was to determine whether the length of the THRA1 microsatellite, which resides in a noncoding portion of the thyroid hormone receptor-alpha1 gene, affects receptor expression and is linked to clinicopathological parameters in thyroid cancer. EXPERIMENTAL DESIGN: In 30 cases of surgically resected sporadic thyroid cancer, the length of the THRA1 microsatellite was determined by DNA sequence analysis, and expression of thyroid hormone receptor-alpha1 was assessed immunohistochemically in thin sections cut from tumor blocks. The length of THRA1 and expression of thyroid hormone receptor-alpha1 were also assessed in seven cancer cell lines. Regression analysis was used to gauge the correlation between the size of THRA1 and receptor expression. Multivariate analysis was used to test for links to the clinical parameters of gender, age, histology, stage, nodal involvement, distant metastasis, extrathyroidal invasion and tumor-node-metastasis (TNM) classification. RESULTS: A statistically significant correlation between the length of THRA1 and thyroid hormone receptor-alpha1 expression was observed in both cell lines and primary thyroid cancers. Thyroid tumors that displayed higher than average thyroid hormone receptor-alpha1 expression had expanded THRA1 microsatellites and were less aggressive as judged by TNM ranking. A statistically significant correlation was also found between low thyroid hormone receptor-alpha1 expression and more aggressive thyroid cancer, as judged by extrathyroidal invasion and nodal involvement. CONCLUSIONS: Less aggressive thyroid cancer was found to be linked to increased thyroid hormone receptor-alpha1 expression and an expanded THRA1 microsatellite.
AB - PURPOSE: The purpose of this study was to determine whether the length of the THRA1 microsatellite, which resides in a noncoding portion of the thyroid hormone receptor-alpha1 gene, affects receptor expression and is linked to clinicopathological parameters in thyroid cancer. EXPERIMENTAL DESIGN: In 30 cases of surgically resected sporadic thyroid cancer, the length of the THRA1 microsatellite was determined by DNA sequence analysis, and expression of thyroid hormone receptor-alpha1 was assessed immunohistochemically in thin sections cut from tumor blocks. The length of THRA1 and expression of thyroid hormone receptor-alpha1 were also assessed in seven cancer cell lines. Regression analysis was used to gauge the correlation between the size of THRA1 and receptor expression. Multivariate analysis was used to test for links to the clinical parameters of gender, age, histology, stage, nodal involvement, distant metastasis, extrathyroidal invasion and tumor-node-metastasis (TNM) classification. RESULTS: A statistically significant correlation between the length of THRA1 and thyroid hormone receptor-alpha1 expression was observed in both cell lines and primary thyroid cancers. Thyroid tumors that displayed higher than average thyroid hormone receptor-alpha1 expression had expanded THRA1 microsatellites and were less aggressive as judged by TNM ranking. A statistically significant correlation was also found between low thyroid hormone receptor-alpha1 expression and more aggressive thyroid cancer, as judged by extrathyroidal invasion and nodal involvement. CONCLUSIONS: Less aggressive thyroid cancer was found to be linked to increased thyroid hormone receptor-alpha1 expression and an expanded THRA1 microsatellite.
M3 - Journal article
C2 - 12231529
SN - 1078-0432
VL - 8
SP - 2870
EP - 2874
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 9
ER -
