| Objective: By testing and comparing the expression level of 4 factors(CXCR-4,HGF,VEGF-D and VEGFR-3) in different typing of thyroid tumor(thyroid adenoma, papillary thyroid carcinoma, follicular thyroid carcinoma and medullary thyroid carcinoma) and different clinicopathological factors of PTC(age, sex, size of tumor, stage, lymph node metastasis),the correlation were studied between the 4 factors and invasion,lymph node metastasis and prognosis of PTC. This study will be helpful for consummating the metastatic mechanism of lymph node in PTC,and for screening tumor related markers and designing microarray gene chip to evaluate the potential of tumor metastasis or finding new theory and therapeutic target for effective regimen of interrupting metastasis of PTC,and finally facilitating the indivdualized surgery for cN0 stage of PTC.Method: 70 cases of PTC with complete clinical records and preliminary diagnosis were picked out from patients in Tianjin cancer hospital from 1974 to 1995.The expression of HGF,CXCR-4,VEGF-D and VEGFR-3 in 70 cases of PTC were assayed by using immunohistochemical staining. To study the correlation of the 4 factors and clinicopathological aspects of PTC,statistical analysis was carried out by compiling the expression level with clinicopathological characters in PTC patients and control.Result:1. The rate of immuno-positive staining HGF was 82.86% (58/70)in 70 cases of PTC, 20.00% in 15 cases of thyroid adenomaand 60.00% in 20 cases of PTC, with significant difference between groups(P＜0.05); the positive rate in MTC is 86.67% and without significant difference compared with PTC(P＞0.05);in 70 cases of PTC, the positive expression rate of HGF was 91.30% with lymph node metastasis and 66.67% without metastasis, there are a significant difference between the two groups(P＜0.05),so as to local invasion group and without local invasion group in papillary thyroid carcinoma(P＜0.05).The expression of HGF in papillary thyroid carcinoma was not related to the patients' gender, age, tumor size.2. The rate of immuno-positive staining CXCR-4 was 60.00% (42/70) in 70 cases of PTC, 13.33% in 15 cases of thyroid adenoma and 30.00% in 20 cases of PTC, with significant difference between groups(P＜0.05); the positive rate in MTC is 60.00 % and without significant difference compared with PTC(P＞0.05);in 70 cases of PTC, the positive expression rate of CXCR-4 was 71.74% with lymph node metastasis and 37.50% without metastasis, there are a significant difference between the two groups(P＜0.05),so as to local invasion group and without local invasion group in papillary thyroid carcinoma(P＜0.05).The expression of CXCR-4 in papillary thyroid carcinoma was not related to the patients' gender, age, tumor size.3. The rate of immuno-positive staining VEGF-D was 71.43 % (50/70) in 70 cases of PTC, 6.67% in 15 cases of thyroid adenoma and 25.00% in 20 cases of PTC, with significant difference between groups(P＜0.05); the positive rate in MTC is 66.67 % and without significant difference compared with PTC(P＞0.05);in 70 cases of PTC, the positive expression rate of VEGF-D was 89.13%with lymph node metastasis and 37.50% without metastasis, there are a significant difference between the two groups(P＜0.05), the positive expression rate of VEGFR-3 and lymph vessel density were 86.96%,14.50±3.27 with lymph node metastasis and 354.17%,8.08±2.49 without metastasis, there are a significant difference between the two groups(P＜0.05).4. The rates of simultaneous immuno-positive staining of VEGF-D and CXCR-4 in 70 papillary thyroid carcinoma were 55.71%(39/70).The positive relationship has been found between the expression status of VEGF-D and CXCR-4 and cervical lymph node metastasis.Conclusions:1. HGF and CXCR-4 might be useful to evaluate the biological behavior of local invasion and prognosis of PTC;2. The function of CXCR-4 may promote lymph node metastasis of PTC by affecting the migration ability of carcinoma;3. HGF might promote lymph node metastasis of PTC;4. VEGF-D and VEGFR-3 might cause lymph node metastasis of PTC by lymphangiogenesis;they are useful for evaluating the metastasis and prognosis of PTC.5. The expressions of VEGF-D was correlated with the expressions of CXCR-4 in PTC,the patients with VEGF-D positive and CXCR-4 positive had the high possibility of lymph node metastasis6. The expressions of HGF, VEGF-D,VEGFR-3,CXCR-4 were correlated with lymph node metastasis in MTC;7. There are high positive expression of HGF, VEGF-D,VEGFR-3,CXCR-4 of PTC.Combining detection of the expression of HGF, VEGF-D, VEGFR-3, CXCR-4 might be useful to evaluate the biological behavior of PTC;8. The process of lymph node metastasis of PTC need multi-factor and multi-procedure,and growth factor,chemokine and lymphangiogenesis might participated in this process.
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