三叶因子3和SDF-1/CXCR4生物轴在甲状腺乳头状癌中的表达及临床意义

目的：研究三叶因子3、基质细胞衍生因子-1（SDF-1）及其受体CXCR4在甲状腺乳头状癌（PTC）,中的表达,探讨三者在乳头状癌发生、发展和转归中的作用及相关性。方法：应用免疫组织化学法（SP法）检测92例PTC及癌旁组织中TFF3、SDF-1及CXCR4的表达,采用图像分析软件系统对免疫组织化学结果进行半定量分析。结果：①TFF3蛋白表达于癌细胞胞质,癌旁滤泡上皮细胞TFF3阴性或弱阳性,TFF3阳性率92.39%,其中临床Ⅲ~Ⅳ期强阳性率为71.19%（42/59）,Ⅰ~Ⅱ期强阳性率为33.33%（11/33,P〈0.01）;有淋巴结转移者明显高于无淋巴结转移者（100.00%vs 86.27%,P〈0.05）。TFF3的AOD值在PTC内高于癌旁、有淋巴结转移者高于无淋巴结转移者、临床Ⅲ~Ⅳ期高于Ⅰ~Ⅱ期（P〈0.05或P〈0.01）。②SDF-1表达于胞质,转移淋巴结和癌旁细胞为弱阳性或阴性。SDF-1阳性率和AOD值在PTC内高于癌旁、有淋巴结转移者高于无淋巴结转移者、临床Ⅲ~Ⅳ期高于Ⅰ~Ⅱ期、45岁以上高于45岁以下者（P〈0.05或P〈0.01）;CXCR4主要表达于胞质,少数表达于胞核,癌旁组织中呈弱阳性或阴性,PTC中CXCR4表达的阳性率和AOD值与SDF-1相似：癌内高于癌旁、与临床分级、淋巴结转移和年龄有关（P〈0.05或P〈0.01）。③PTC中,TFF3与SDF-1蛋白、SDF-1与CXCR4蛋白表达水平呈正相关（r=0.971,P〈0.01）。结论：TFF3、SDF-1、CXCR4在PTC中的高表达与癌的发生、发展有关,对判断PTC的恶性程度和病情进展有重要价值。

The expression and significance of trefoil factor 3 and SDF-1/CXCR4 biological axis in papillary thyroid carcinoma

Objective：To study the expression of trefoil factor 3（TFF3）with stromal cell-derived factor（SDF- 1） and its receptor （CXCR4） in papillary thyroid carcinoma（PTC）, and investigate the function of TFF3,SDF-1/ CXCR4 and the relationship among them during the tumor genesis,development and outcome of PTC. Method：De- tecting the expression of TFF3 and SDF-1/CXCR4 by immunohistochemieal method（SP） in 92 cases of PTC and para-earcinoma tissue. Semiquantitative analysis of the results of immunohistochemistry was conducted by image analysis software. Result： @TFF3 protein was expressed in the cytoplasm of cancer cells, while TFF3 was negtive or weakly positive in folieular cells of para-carcinoma tissue. The positive expression rate of TFF3 was 92.39% ,of which the strong positive rate of clinical stage ]]I --iV accounted for 71.79~ （42/59） and that of clinical stage I -- II was 33.33%（11/33）（P＊~0. 01）. The positive rate of TFF3 was significantly higher in the cases with lymph node metastasis than those without lymph node metastasis（100.00~ vs 86. 270/00 ,P（0.05）. The AOD value of TFF3 was higher in PTC than in para-carcinoma tissue, that in cases with lymph node metastasis was higher than those without lymph node metastasis, and that in stage ]]I- IV was higher than those in I -- ]I （P（0.05 or P（ 0.05）. ~There was high expression of SDF-1 in the cytoplasm of malignant tissues. The para-carcinoma tissue was weakly positive or negative to SDF 1 and metastatic lymph nodes was weakly positive to SDF 1. The positive rates and AOD values of SDF-1 protein were similar to those of TFF3 in PTC,that is to say the positive rate and AOD values were higher in PTC than in para-carcinoma tissue, those in cases with lymph node metastasis were higher than those without lymph node metastasis, those in stage m - 1v were higher than those in I - II, and those in patients older than 45 years＂ old was obviously higher than those in patients under 45 years＂ old（P〈0.05 or P〈0.01）;CXCR4 was also mainly expressed in cytoplasm with few expression in nuclei, while negative or weakly positive in para-carcinoma. The positive rate and AOD values of CXCR4 in PTC were similar to SDF-1, meaning that they were higher in PTC than in para-carcinoma tissue and associated with the clinical stage, lymph node metastasis and age（P〈0.05 or P〈0. 01）. @There was positive relationship between TFF3 and SDF-1 as well as between SDF-1 and CXCR4 in PTC（r=0. 971 ,P〈O. 01）. Conclusion：The high expression of TFF3 ,SDF-1 and CXCR4 in PTC are correlated with carcinogenesis and progression, and may play a significant role in evalua- ting the malignancy degree and progression of PTC.