Role of Interleukin-18 in Thyroid tumorigenesis

Abstract

Purpose: Although the significance of Interleukin-18 (IL-18) has been studied in pathogenesis of different cancers including, ovarian, gastric, breast, lung carcinoma and melanoma, its role in thyroid cancer- the most common endocrine malignancy has not yet been looked at extensively. Hence, this study intended to examine the role of IL-18 in thyroid tumorigenesis. Methods: Sixty seven patients with benign thyroid diseases and 106 thyroid cancer patients (including 83 papillary, 6 follicular, 9 medullary and 8 anaplastic thyroid carcinoma patients) were enrolled in the study. To accomplish the aim, the circulating levels of IL-18 were estimated by enzyme linked immunosorbent assay (ELISA) from all patients and compared with controls. Further, protein expression of IL-18 was determined from the primary tumors of the patients using immunohistochemistry. Results: It was observed that the circulating levels of IL-18 were significantly higher in all patients: benign thyroid diseases ( p = 0.006), papillary ( p < 0.001), follicular ( p = 0.023), medullary ( p = 0.002) and anaplastic thyroid cancer ( p < 0.001) than the controls. In addition to this, IL-18 could well discriminate papillary (AUC = 0.627, p =0.008) and anaplastic thyroid carcinoma patients (AUC = 0.777, p = 0.011) from patients with benign thyroid diseases. However, the difference between tumoral protein expression of IL-18 in patients with benign thyroid diseases and thyroid carcinoma was not significant. The Kaplan - Meier survival analysis revealed that neither the circulating nor the tumoral protein expression of IL-18 was the significant predictor of disease free survival (DFS) or overall survival (OS) in papillary thyroid cancer patients. Conclusion: Though not a significant prognosticator, circulating IL-18 may be useful as a differentiating factor in thyroid tumorigenesis and the increase in serum IL-18 levels may be provoked in response to the tumor. Thus, including IL-18 along with the current treatment practice may have a significant role in better management of the disease. However, further exploration of this interleukin is required in a larger series of patients with longer follow up period.