The Study On The Relationship Between The Lymphangiogenesis And The Lymphatic Metastasis In Thyroid Neoplasm

Objective: The thyroid neoplasm is one of the most commonendocrine carcinoma in clinic, and the incidence of the disease is about 4%-7%,including 5% of malignant disease. The patients suffered from thyroidcarcinoma are increasing recently, which threat the human's life dramatically.The metastasis is the most basic and important feature of the malignant tumorand influence the prognosis of the patient. Along with the finding of theVEGF-C, D, their receptor VEGRR-3 and the special marker of the lymphaticendothelial cell, the relationship between the lymphangiogenesis and themetastasis has become the focus of the tumor study. There are some studieswhich revealed that the expression of VEGF-C, VEGFR-3 is correlated with thehistopathology classification and metastasis tightly in thyroid neoplasm. TheLYVE-1 is acknowledged as a special marker of the lymphatic endothelial cell.There is no report on the expression of LYVE-1 in thyroid neoplasm, as well asthe systematic study on the relationship between the expression of VEGF-C,VEGFR-3, LYVE-1 and the lymphatic metastasis in benign and malignantthyroid tumor. This study was designed to compare the difference of theexpression of VEGF-C, VEGF-3 and LYVE-1 in benign and malignant thyroidtumor with or without lymphatic metastasis, and explore the relationshipbetween the diversification of the lymphangiogenesis and the metastasis toprovide the theoretic proof to predict the prognosis of this kind of disease.Methods: 135 pieces of paraffin embedding sections of thyroid neoplasm werechosen in this study, and there were 30 cases of thyroid adenoma, 28 cases ofpapillary thyroid carcinoma, 23 cases of medullary thyroid carcinoma, 27 casesof follicular thyroid carcinoma, 17 cases of anaplastic thyroid carcinoma and 10pieces of normal thyroid tissue were used as negative control. There were 21cases with lymphatic metastasis. The expression of VEGF-C, VEGFR-3, andLYVE-1 were tested by immunohistochemistry, and the expression of themRNA of VEGF-C was tested by TUNEL. All data in different neoplasm wasanalysed in the end. Results: ①The positive expression rate of VEGF-C andVEGF-C mRNA is 82.6% and 86.2% separately in thyroid carcinoma tissue,and 68.8% and 72.9% separately in normal thyroid tissue. The P value is 0.006and 0.004 which show statistic different, and the expression level of VEGF-Cand VEGF mRNA in thyroid carcinoma are higher than normal thyroid tissue.The expression of VEGF-C in thyroid carcinoma with lymphatic metastasis is95.0% compare with 79.1% in thyroid carcinoma without lymphaticmetastasis(p=0.002). The positive expression rate of VEGF-C and VEGF-CmRNA in follicular thyroid carcinoma are 92.1% and 94.7%, 70.0% and 70.0%in medullary thyroid carcinoma, and 66.7% and 75.0% in anaplastic thyroidcarcinoma. The different of the expression between follicular thyroid carcinomaand medullary thyroid carcinoma, as well as the different between follicularthyroid carcinoma and anaplastic thyroid carcinoma are statisticaldifferent.②The positive expression rate of VEGFR-3 in thyroid carcinomatissue is 90.8%, while 75.0% in thyroid adenoma tissue. There is statisticaldifference between the two group(p=0.000).In thyroid carcinoma cases, thepositive expression rate of VEGRR-3 in the tissue of patients with lymphaticmetastasis is 100%, while 88.1% in the tissue of patients without lymphaticmetastasis, and the difference is statistical. In the tissue of the differentpathological classification of thyroid carcinoma, the positive expression rate ofVEGFR-3 in follicular thyroid carcinoma is 97.4%, 80.0% in medullary thyroidcarcinoma and 83.3% in anaplastic thyroid carcinoma. The expressiondifference between follicular and medullary thyroid carcinoma isstatistical(p=0.002), as well as the difference between follicular and anaplasticthyroid carcinoma(p=0.001). ③ The lymphatic microvessel density withLYVE-1 marking in thyroid carcinoma is 8.79±6.52, and 3.8±1.2 in thyroidadenoma, and there is statistic difference between each group(t=6.9291,P=0.000).The lymphatic microvessel density is thyroid carcinoma is higherthan adenoma. In thyroid carcinoma, the lymphatic microvessel density in thesample with lymphatic metastasis is 12.2±7.2,while in the sample withoutlymphatic metastasis is 7.8 ± 6.4 , and the difference isstatistical(t=2.6214,P=0.0104). In the tissue of the different pathologicalclassification of thyroid carcinoma,the lymphatic microvessel density infollicular thyroid carcinoma is 11.4±8.6,4.2±2.4 in medullary thyroidcarcinoma and 4.8±1.8 in anaplastic thyroid carcinoma. The differencebetween follicular and medullary thyroid carcinoma is statistical(t=2.6020,P=0.0124),and the difference between follicular and anaplastic thyroidcarcinoma is statistical(t=2.6227,P=0.0117).④The correlation analysis of theexpression of VEGF-C,VEGFR-3,VEGF-C mRNA and LYVE-1show: Thereis correlation between thyroid carcinoma and thyroid adenoma(r=0.84,P=0.020),and correlation between thyroid carcinoma with or without lymphaticmetastasis (r=0.87,P=0.001),and correlation between follicular and medullarthyroid carcinoma(r=0.85,P=0.032), and correlation between follicular andanaplastic thyroid carcinoma( r=0.86,P=0.027). CONCLUSIONS: There isdifferent expression degree of VEGF-C,VEGFR-3 and LYVE-1 in thyroidneoplasm, and higher expression in thyroid carcinoma than thyroid adenoma. Inthyroid carcinoma, the expression degree from high to low is papillary,anaplastic, follicular and medullar thyroid carcinoma. The expression degree ishigher in thyroid carcinoma with lymphatic metastasis than without lymphaticmetastasis. It is convinced that the lymphangiogenesis is tightly correlation withlymphatic metastasis in thyroid neoplasm.