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Microsatellite Instability in Thyroid Cancer

Hot Spots, Clinicopathological Implications, and Prognostic Significance¹

The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California, 92037 [M. O., I. N., S. S., C-H. B., S. St., D. L., N. R.], and Department of Surgery II, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan. [M. O., I. N., S. S., S. T.]

Purpose: To determine whether microsatellite instability (MSI) in particular loci has clinicopathological significance in thyroid cancer.

Experimental Design: Seventy-six cases of surgically resected thyroid cancer were screened for MSI at nine microsatellites: THRA1, TSHR, D2S123, D11S912, D2S115, D2S399, p53, RET, or BAT-26. Multivariate analysis was performed to test for links between MSI and the clinical parameters of gender, age, histology, stage, nodal involvement, and prognosis.

Results: THRA1, residing in the thyroid hormone receptor gene, displayed the highest levels of MSI at 36.5%. MSI in TSHR, located within the thyroid-stimulating hormone receptor gene, was found to be linked to cancer in the elderly (>70 years of age) and with high-grade (N 3, 4) nodal involvement. In follicular cancer, MSI in D2S123 occurred at a frequency of 100% (7/7) with no (0%) occurrence of MSI at the nearby D2S115, D2S399, or BAT-26 loci. Regarding prognosis, patients with MSI-positive cancer showed better long-term survival. BAT-26, which is an important marker in colorectal cancer, displayed the lowest frequency of MSI in our panel of thyroid tumors.

Conclusion: Whereas patients with MSI-positive cancer showed better long-term survival, as is the case for colorectal cancer, our finding of the low frequency of MSI in BAT-26 suggests that the biochemical defects governing the spectrum of MSI in thyroid and colorectal cancer are different. MSI in THRA1, TSHR, and D2S123 appears to be an integral part of thyroid carcinogenesis, as evidenced by the high frequency of MSI and significant correlation to clinical data.

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