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

Abstract

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 ¼ 0.027) and VEGF-D immunoreactivity (P ¼ 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.

Role of vascular endothelial growth factor receptor-3/Flt-4 in early-stage cervical cancer

“…VEGFR-3/Flt-4-positive vascular density (MVD) was found to be correlated to the clinical stage of the cancers and the expression of VEGF-C and VEGF-D, but was unrelated to menstrual status, histological grade and other clinicopathological factors. These results differed from Yasuoka et al (5) due to the fact that VEGFR-3/Flt-4 plays an important role in the regulation of tumor lymphangiogenesis and angiogenesis. VEGF-C and VEGF-D are secreted by cancer cells and show a paracrine action on the TK receptor (VEGFR-3/ Flt-4), which is expressed in lymphatic and vascular endothelial cells to mediate proliferation and differentiation of endothelial cells and lumen formation.…”

Renal lymphatics, and lymphatic involvement in sinus vein invasive (pT3b) clear cell renal cell carcinoma: a study of 40 cases

“…[8][9][10][11] This has enabled investigators to investigate the incidence and prognostic importance of lymphatic invasion in a number of cancers, and has led to the identification of tumor-associated lymphangiogenesis. [12][13][14][15][16] Renal cell carcinoma has not been previously examined for lymphatic invasion using lymphatic-specific markers. In this study, 40 cases of sinus vein invasive clear cell renal cell carcinoma (CC) have been examined for lymphatic involvement.…”

Liposomal honokiol inhibits VEGF‐D‐induced lymphangiogenesis and metastasis in xenograft tumor model

“…Some animal studies have shown that the expression of VEGF-D promotes lymphangiogenesis and metastatic spread of tumor cells via lymphatics in papillary thyroid carcinoma, 30 lung cancer, 31 gastric cancer 32 and pancreatic beta-cell carcinogenesis. 33 However, most studies are based on cultured tumor cells, little shows a correlation between high VEGF-D levels and lymph node metastasis in xenograft lung carcinoma.…”