Endocrine Abstracts

Background: Altered circadian clock characteristics have been shown in malignant thyroid nodules. REV-ERB-alpha is a circadian clock component that functions as a transcriptional repressor which coordinates circadian rhythm and cell metabolism. However, the protein expression of REV-ERB-alpha has not been properly investigated.

Methods: Immunohistochemical analysis was performed on our in-house tissue microarrays. Immunoreactivity was evaluated using H-scores calculated by multiplying stain intensity by the percentage of positive stained cells. Recurrence-free survival was determined using a Kaplan-Meier curve.

Results: A total of 142 cases with differentiated thyroid cancer were evaluated. Nuclear staining of REV-ERB-alpha was upregulated in follicular epithelial cells of thyroid cancer but was absent in their normal counterparts. The H-scores were positively correlated with patients’ age at diagnosis (Spearman’s rank correlation rho = 0.310, P= 0.0002). Furthermore, increasing H-scores were associated with extrathyroidal extension (Jonckheere-Terpstra trend test, P= 0.0005), lymph node metastasis (P= 0.036), and tumor-node-metastasis stage (P= 0.001). Patients with higher REV-ERB-alpha expression in the tumor had a shorter recurrence-free survival (log-rank test, P= 0.018).

Conclusion: Thyroid cancer exhibits overexpression of REV-ERB-alpha. Nuclear expression levels have a prognostic significance in differentiated thyroid cancer.