Strong immunoexpression of midkine is associated with multiple lymph node metastases in BRAFV600E papillary thyroid carcinoma.

Midkine is a multifunctional, heparin-binding growth factor that is frequently expressed in patients with malignancies but is undetectable in healthy adults. In various cancers, high expression of midkine is associated with aggressive clinical behavior and a poor prognosis. In the present study, we investigated the expression of midkine in papillary thyroid carcinoma (PTC) and assessed its association with a BRAFV600E mutation and the clinicopathological parameters. We determined the presence of a BRAFV600E mutation in 79 cases of PTC and examined the effects of the BRAFV600E mutation on midkine expression in primary thyrocytes. In addition, we evaluated the association between midkine expression and various clinicopathological parameters. We found that midkine is more frequently expressed in BRAFV600E PTC (68.3%) than in BRAF wild-type PTC (18.8%). BRAFV600E transduction could up-regulate midkine expression in primary thyrocytes. Moreover, midkine expression was associated with multiple lymph node (≥5) metastases in BRAFV600E PTC. In conclusion, our results suggest that midkine expression could be a clinically useful marker in predicting the presence of multiple lymph node metastases in BRAFV600E PTC.