Micro-Lymphatic Vessel Density In Thyroid Papillary Carcinoma: Correlation With VEGF-C Expression And Cervical Lymphatic Metastasis

Objective To assess the expression of the lymphangiogenic factor vascularendothelial growth factor C (VEGF-C), and D2-40, a novel lymphatic vessel marker,in thyroid papillary carcinoma and their relationship to the cervical lymh nodesmetastasis.Methods Micro-lymphatic vessel density (MLVD) was measured in 60 cases ofthyroid papillary carcinoma and 25 cases of nodular goiter using a novel lymphaticmarker D2-40 immunohistochemically. The relationship in MLVD,cervical lymphnode metastasis were evaluated in detail, and the expression of both mRNA andprotein level of VEGF-C in tumor were performed by immunohistochemistry andRT-PCR.ResultsAlmost all (54/60 cases, 90.0%) were D2-40 negative, without lymph vessel at all in the stroma of papillary thyroid carcinoma, we have found significantly higher MLVD in the periphery of the tumor than goiter cases (13.32±2.56 vs.4.21±1.82, P< 0.01).MLVD was also significantly higher relativity to lymph node positive group than in lymph node negative group (18.16±2.23 vs.ll.73±2.34, P<0.05). 23 cervical lymph node metastasis cases in the background of 29 cases lymph vessel invasion (LVI) were found, while only 10 in 31 cases without LVI, which correlated with MLVD and there is significant relationship in them.VEGF-C was positive (49/ 60, 81.7%)in papillary thyroid carcinoma and (6/ 25, 25.0% ) goiter, significant difference was obtained statistically. Same positive result of VEGF-C was found in 31/ 33 cases (93.4%) cervical lymph node metastasis and in 18/27 cases (66.7 %) of group without cervical metastasis.The expression of VEGF-C mRNA level was significant high in the group of papillary thyroid carcinoma cases than the cases of goiter group (P<0. 05) and the same result within cervical lymph node metastasis and none metastasis groups. Butthere was no relationship compared with MLVD (P>0.05). Conclusion1. D2-40 is an excellent lymphatic endothelial marker with high specificity andsensitivity for research and with its perfect quality of non cross-reaction with angioendothelial marker CD34.2. D2-40 positive tumor lymphgenesis was predominately in the periphery of the papillary thyroid carcinoma, while there was no lymph vessel was found in the intratumor.3. MLVD in papillary thyriod carcinoma was correlated with lymphatic vessel invasion and cervical lymphatic metastasis.4. Both mRNA and protein expression of VEGF-C is significantly higher in thyroid papillary carcinoma with cervical lymphatic metastasis and it is a possible role in tumor lymphogensis.