Expression of the Sonic Hedgehog pathway molecules in synchronous follicular adenoma and papillary carcinoma of the thyroid gland in predicting malignancy

Background: Recent studies have shown that the Sonic Hedgehog pathway plays an important role in tumorigenesis and cancer proliferation. The Sonic Hedgehog pathway is required for normal thyroid gland development, but when activated as a result of gene mutation or overexpression, it may stimulate thyroid tumor cell proliferation. This study determines whether 3 molecules, Patched, Smoothened, and Sonic Hedgehog, involved in the Sonic Hedgehog pathway are overexpressed equally in synchronous follicular thyroid adenoma and papillary thyroid carcinoma. Methods: Eighteen patients with synchronous follicular thyroid adenoma and papillary thyroid carcinoma underwent thyroidectomy. Immunohistochemistry was performed on the paraffin-embedded tissue to detect expression of Patched, Smoothened, and Sonic Hedgehog in both tumor types. The expression in these neoplasms was graded by 2 observers. Results: Five patients had insufficient tumor tissue and were removed from the analysis. Patched expression was detected in 5 of 13 (38%) follicular adenomas and 5 of 12 (42%) papillary carcinomas. Smoothened was expressed in 4 of 13 (31%) follicular adenomas and 3 of 13 (23%) papillary carcinomas. Sonic Hedgehog was expressed in 4 of 13 (31%) follicular adenomas and 11 of 13 (85%) papillary carcinomas. Conclusion: Expression of the 3 molecules involved in the Sonic Hedgehog pathway was similar in follicular thyroid adenoma, but Sonic Hedgehog expression was a more sensitive indicator of malignancy in papillary thyroid carcinoma. The Sonic Hedgehog molecule may become a diagnostic marker when the cytologic or histologic features are not characteristic of a papillary carcinoma. Greater understanding of the Sonic Hedgehog pathway may provide molecular methods for preventing or treating papillary thyroid carcinoma.