Expression of GLP-1 receptor and CD26 in human thyroid C-cells: The association of thyroid C-cell tumorigenesis with incretin-based medicine

Recent reports have demonstrated that long‑term and high dosage treatments with incretin-based medicine, such as hormone glucagon‑like peptide‑1 (GLP‑1) may induce thyroid C‑cell pathological changes in rodents, rather than in humans. Doubts regarding the tumorigenic potential of GLP‑1 analogues in human thyroid C‑cells remain. The present study aimed to determine the expression levels of GLP‑1 receptor (GLP‑1R) and cluster of differentiation 26 (CD26) in the C‑cells of thyroid tissues from non‑neoplastic, medullary carcinoma and hyperplasia subjects, and to explore the potential clinical significance. The following cases were analyzed: Medullary thyroid carcinoma (n=62, including 59 paraffin-embedded samples and 3 fresh frozen samples), C‑cell hyperplasia (n=20, paraffin‑embedded samples) and non-neoplastic thyroid tissue samples (n=7, paraffin‑embedded samples). GLP‑1R and CD26 expression was detected using immunohistochemical staining and western blotting. There were significant differences in the expression levels of the two markers between medullary thyroid carcinoma and C‑cell hyperplasia, in addition to between medullary thyroid carcinoma and non‑neoplastic thyroid tissue following immunohistochemical staining. Similar significant differences in the expression of GLP‑1R and CD26 were detected using western blot analysis in the medullary thyroid carcinoma compared with non‑neoplastic thyroid tissue sectioned from the aforementioned fresh frozen samples. There was a significant negative correlation between GLP‑1R and CD26 expression. In addition, the present data indicated that GLP‑1R expression was associated with the age of the patients with medullary thyroid carcinoma. These results suggested that GLP-1R and CD26 may be closely associated with the development of thyroid C‑cell hyperplasia and medullary thyroid carcinoma, and indicated the importance of being aware of the side effects of incretin medicine.