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Clinical Cancer Research Vol. 8, 2870-2874, September 2002
© 2002 American Association for Cancer Research


Molecular Oncology, Markers, Clinical Correlates

Expansion of Microsatellite in the Thyroid Hormone Receptor-{alpha}1 Gene Linked to Increased Receptor Expression and Less Aggressive Thyroid Cancer1

Masamitsu Onda, Daisy Li, Shinichi Suzuki, Izumi Nakamura, Seiichi Takenoshita, Carl-Henrik Brogren, Sabina Stampanoni and Nicholas Rampino2

The Burnham Institute, La Jolla, California 92037 [M. O., D. L., S. Su., I. N., C-H. B., S. St., N. R.], and Department of Surgery II, Fukushima Medical University, Fukushima 960-1295, Japan [S. T.]

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-{alpha}1 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-{alpha}1 was assessed immunohistochemically in thin sections cut from tumor blocks. The length of THRA1 and expression of thyroid hormone receptor-{alpha}1 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-{alpha}1 expression was observed in both cell lines and primary thyroid cancers. Thyroid tumors that displayed higher than average thyroid hormone receptor-{alpha}1 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-{alpha}1 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-{alpha}1 expression and an expanded THRA1 microsatellite.




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A. Baida, S. M. Farrington, P. Galofre, R. Marcos, and A. Velazquez
Thyroid Cancer Susceptibility and THRA1 and BAT-40 Repeats Polymorphisms
Cancer Epidemiol. Biomarkers Prev., March 1, 2005; 14(3): 638 - 642.
[Abstract] [Full Text] [PDF]




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Copyright © 2002 by the American Association for Cancer Research.