Expansion of microsatellite in the thyroid hormone receptor-alpha1 gene linked to increased receptor expression and less aggressive thyroid cancer.
OBJECTIVE
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.


METHODS
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.
Onda
Masamitsu
M
The Burnham Institute, La Jolla, California 92037, USA.
Li
Daisy
D
Suzuki
Shinichi
S
Nakamura
Izumi
I
Takenoshita
Seiichi
S
Brogren
Carl-Henrik
CH
Stampanoni
Sabina
S
Rampino
Nicholas
N
D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018895:Microsatellite Repeats; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000378:metabolism
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011988:Receptors, Thyroid Hormone