VEGF-D expression and lymph vessels play an important role for lymph node metastasis in papillary thyroid carcinoma

Papillary thyroid carcinoma frequently metastasizes to regional lymph nodes, and lymph node metastasis increases the risk of local regional relapse. Recent evidence suggests that vascular endothelial growth factor-D (VEGF-D) promotes lymphangiogenesis, which in turn promotes lymphatic metastasis. Therefore, the role of VEGF-D messenger RNA transcript levels and VEGF-D immunoreactivity in lymph node metastasis in papillary thyroid carcinoma was investigated. In addition, the role of blood vascular vessel, lymph vessel, and Flt-4-positive vessel densities were studied in relation to their suspected association with lymph node metastasis, and with VEGF-D expression. VEGF-D messenger RNA transcript levels by quantitative real-time reverse transcription-polymerase chain reaction and VEGF-D immunoreactivity by immunohistochemistry in 49 papillary thyroid carcinomas were also studied. This was followed by quantitative immunohistochemical staining for CD34, podoplanin, and Flt-4. Lymph node metastasis was significantly correlated with VEGF-D messenger RNA transcript levels (P=0.027) and VEGF-D immunoreactivity (P=0.019). Increased lymph vessel density was also correlated with VEGF-D expression and lymph node metastasis. In conclusion, our findings indicate that VEGF-D expression and increased lymph vessel density may have an important role for lymph node metastasis in papillary thyroid carcinoma.