[三叶因子3及SDF-1/CXCR4生物学轴在甲状腺乳头状癌中的表达及意义]

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

作者信息

Xue Gang, Huang Jing, Zhang Huiqin, Zhang Wenjing, Wu Jingfang, Shang Xiaoling

出版信息

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014 Jan;28(2):108-12.

Abstract

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

Detecting the expression of TFF3 and SDF-1/CXCR4 by immunohistochemical method (SP) in 92 cases of PTC and para-carcinoma tissue. Semiquantitative analysis of the results of immunohistochemistry was conducted by image analysis software.

RESULT

(1) TFF3 protein was expressed in the cytoplasm of cancer cells,while TFF3 was negative or weakly positive in follicular cells of para-carcinoma tissue. The positive expression rate of TFF3 was 92.39%, of which the strong positive rate of clinical stage III-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 86.27%, 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 III-IV was higher than those in I-II (P < 0.05 or P < 0.05). (2) 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 III-IV 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). (3) There was positive relationship between TFF3 and SDF-1 as well as between SDF-1 and CXCR4 in PTC (r = 0.971, P < 0.01).

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 evaluating the malignancy degree and progression of PTC.

摘要

目的

研究三叶因子3（TFF3）与基质细胞衍生因子（SDF-1）及其受体（CXCR4）在甲状腺乳头状癌（PTC）中的表达情况，探讨TFF3、SDF-1/CXCR4在PTC发生、发展及预后中的作用及其相互关系。

方法

采用免疫组织化学SP法检测92例PTC组织及癌旁组织中TFF3和SDF-1/CXCR4的表达，应用图像分析软件对免疫组化结果进行半定量分析。

结果

（1）TFF3蛋白在癌细胞胞质中表达，而在癌旁组织滤泡细胞中呈阴性或弱阳性。TFF3阳性表达率为92.39%，其中临床Ⅲ-Ⅳ期强阳性率占71.79%（42/59），临床Ⅰ-Ⅱ期为33.33%（11/33）（P<0.01）。有淋巴结转移病例的TFF3阳性率明显高于无淋巴结转移者（100.00%比86.27%，P<0.05）。PTC中TFF3的平均光密度（AOD）值高于癌旁组织，有淋巴结转移者高于无淋巴结转移者，Ⅲ-Ⅳ期高于Ⅰ-Ⅱ期（P<0.05或P<0.01）。（2）恶性组织胞质中SDF-1呈高表达，癌旁组织呈弱阳性或阴性，转移淋巴结呈弱阳性。PTC中SDF-1蛋白阳性率及AOD值与TFF3相似，即PTC高于癌旁组织，有淋巴结转移者高于无淋巴结转移者，Ⅲ-Ⅳ期高于Ⅰ-Ⅱ期，年龄>45岁患者明显高于<45岁患者（P<0.05或P<0.01）；CXCR4也主要表达于胞质，核内少见，癌旁组织呈阴性或弱阳性。PTC中CXCR4阳性率及AOD值与SDF-1相似，即高于癌旁组织，与临床分期、淋巴结转移及年龄相关（P<0.05或P<0.01）。（3）PTC中TFF3与SDF-1、SDF-1与CXCR4均呈正相关（r=0.971，P<0.01）。