Expansion of Microsatellite in the Thyroid Hormone Receptor-α1 Gene Linked to Increased Receptor Expression and Less Aggressive Thyroid Cancer

• Published in: Clinical cancer research Vol. 8; no. 9; pp. 2870 - 2874
• Main Authors: ONDA, Masamitsu, LI, Daisy, SUZUKI, Shinichi, NAKAMURA, Izumi, TAKENOSHITA, Seiichi, BROGREN, Carl-Henrik, STAMPANONI, Sabina, RAMPINO, Nicholas
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-09-2002
• Subjects: Biological and medical sciences; Endocrinopathies; Malignant tumors; Medical sciences; Thyroid. Thyroid axis (diseases); Endocrinopathy; Human; Prognosis; Nucleotide sequence; Tumoral tissue; Thyroid diseases; Biological marker; Malignancy; Thyroid gland; Metastasis; Malignant tumor; Gene expression; Gene; Microsatellite DNA; DNA; Tumor progression; Genetics; Thyroid hormone; Predictive factor; Aggressiveness; Hormonal receptor
• ISSN: 1078-0432; 1557-3265

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-α1 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-α1 was assessed immunohistochemically in thin sections cut from
tumor blocks. The length of THRA1 and expression of thyroid hormone receptor-α1 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-α1 expression was observed
in both cell lines and primary thyroid cancers. Thyroid tumors that displayed higher than average thyroid hormone receptor-α1
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-α1 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-α1 expression and an expanded
THRA1 microsatellite.