Relationship between the Expression of BRAF V600E and Ki-67 with the Recurrence of Well-Differentiated Thyroid Cancer

OBJECTIVE: This study aims to determine the relationship between BRAF V600E and Ki-67 expression with the recurrence of well-differentiated thyroid cancers. METHOD: The design of this study is a case-control and survival analysis. The data was taken from the thyroid cancer registry in Padang, Indonesia, where samples were taken from well-differentiated thyroid cancer patients who underwent therapy according to the protocol between 2015 and 2020. During this period, 396 well-differentiated thyroid cancer cases were obtained, of which 24 cases experienced recurrence. Of the cases that recurred, we found as many as 20 cases with complete tissue preservation documents later designated as cases. Calculating the expression of BRAF V600E and Ki-67 was performed semi-quantitatively per 100 tumor cells at random. For statistical tests, chi-square and survival analysis were performed using Kaplan-Meier and Cox regression analysis using a computer program with a determined significance level of p < 0.05. RESULT: BRAF V600E expression was found in all cases and controls in which 85% of cases had vigorous intensity and 15% had moderate intensity. Ki-67 expression was found positive in 35% of the recurrent cases, while in control, there was no expression of Ki-67. Patients with positive Ki-67 expression had shorter median survival than patients with negative Ki-67 expression of 40 months (95% CI 35-45 months) to 60 months (95% CI 53-67 months). An association was obtained between Ki-67 expression and thyroid cancer recurrence based on disease-free survival (p<0.05) with HR 1.34 (95% CI 1.13-1.92). CONCLUSION: This study confirms the association between Ki-67 expression and thyroid cancer recurrence based on disease-free survival and can be used as alternative to support the significance of Ki-67 as a predictor of thyroid cancer recurrence. In addition, Ki-67 can complement other molecular markers such as the BRAF V600E, to increase its prognostic strength.