甲状腺乳头状癌组织SDF-1和TFF3表达临床意义分析

目的：分析三叶因子3（trefoilfactor3，TFF3）和基质细胞诱导因子-1（stromalcellderivedfactor1，SDF-1）在甲状腺乳头状癌（papillarythyroidcarcinoma，PTC）和癌旁组织中的表达及意义，为PTC的早期诊断及预后评价提供有价值的资料。方法：采用免疫组织化学和原位杂交技术检测组织芯片（PTC和癌旁各31例）内TFF3、SDF-1蛋白和mR-NA的表达，以SPSS18．0分析其阳性率和平均光密度值与临床病理特征的关系。结果：1）PTC中TFF3蛋白阳性率为83．87%，明显高于癌旁组织25．81％，x2=21．10，P〈0．001；TFF3阳性率与TNM分期（x2=12．30，P〈0．001）和淋巴结转移（x2=5．589，P=0．043）有关。PTC内TFF3的平均光密度（averageopticaldensity，AOD）值为0．49±0．01，高于癌旁0．22±0．06，t=3．448，P〈0．001；有淋巴结转移者为0．57±0．06，高于无淋巴结转移者0．44±0．05，t=2．234，P=0．039；临床Ⅲ／Ⅳ期为0．59±0．07，高于Ⅰ／Ⅱ期0．47±0．05，t=2．167，P=0．041。2）、PTC中SDF-1蛋白阳性率为87．10％，高于癌旁组织16．13％，x2=31．26，P〈0．001；有淋巴结转移者为100．00％，高于无淋巴结转移者75．00％，x2=4．306，P=0．041；临床Ⅲ／Ⅳ期阳性率为100．00％，明显高于临床Ⅰ／Ⅱ期63．64％，x2=8．35，P=0．04；〉45岁为100．00％，明显高于≤45岁63．64％，x2=8．35，P=0．04。癌内SDF-1的AOD值为0．59±0．07，高于癌旁0．28±0．08，t=3．987，P=0．0007；有淋巴结转移者为0．65±0．06，高于无淋巴结转移者0．52±0．05，t=2．458，P=0．009；临床Ⅲ／Ⅳ期为0．66±0．06，高于Ⅰ／Ⅱ期0．50±0．05，t=2．762，P=0．006。3）原位杂交显示，TFF3mRNA和SDF-1mRNA与蛋白表达一致，阳性率虽低于相应蛋白（x2=19．37，P〈0．001），但明显高于癌旁组织，x2=26．35，P〈0．001。4）PTC中TFF3与SDF-1蛋白表达水平呈正相关，r=0．971，P=0．004。5）31例PTC可区分为典型PTC21例（67．74％）、滤泡型7例（22．58％）和高细胞型3例（9．68％）3个亚型。SDF-1和TFF3蛋白阳性率依次为典型PTC（86．96％与86．96％）、滤泡型PTC（85．71％与71．43％）和高细胞型PTC均为100．00％，不同亚型间SDF-1和TFF3阳性率差异无统计学意义；临床Ⅰ／Ⅱ期滤泡型的SDF-1阳性率为83．33％，明显高于典型PTC（0），x2=5．63，P=0．025，临床高细胞型PTC的SDF-1阳性率为100．00％，亦明显高于典型PTC（0），x2=5．00，P=0．046；临床Ⅰ／Ⅱ期高细胞型PTC组织中，TFF3阳性率（100．00％）明显高于典型PTC（0），x2=5．00，P=0．046；临床Ⅲ／Ⅳ期的3种亚型PTC中，SDF-1和TFF3阳性率均为100．00％，差异无统计学意义。结论：TFF3和SDF-1在PTC组织中高表达与癌的发生和发展有关，对判断PTC的恶性程度和病情进展有重要价值，并对Ⅰ／Ⅱ期滤泡型和高细胞型PTC的诊断有指导意义。

Expression and clinical significance of SDF-1 and TFF3 in papillary thyroid carcinoma tissue

OBJECTIVE： To investigate the expression and significance of TFF3 and SDF 1 in papillary thyroid carcinoma（PTC） and para-carcinoma tissues,and provide valuable data for early diagnosis and prognosis of PTC. METHODS： Immunohistochemieal（IHC） SP and in situ hybridization（ISH） were used to detect the expression of TFF3,SDF-1 proteinand mRNA in tissue chip including 31 cases of PTC and para-carcinoma tissues. The positive rate,average optical density （AOD） and the relationship with clinicopathologic features were analyzed by SPSS 18.0. RESULTS： The positive rate of TFF3 protein in PTC was higher than that in para-carcinoma tissues （83.87% vs 25.81% ,x2 =21.10,P〈0. 001）. The positive rate of TFF3 protein in patients with PTC was correlated with the TNM stage and metastasis in lymph nodes （x2 =12.30,P〈0. 001;x2 =5. 589,P=0. 043）. The AOD values of TFF3 was higher in PTC than that in para-carcinoma （0.49±0.01 vs 0. 22±0.06;t=3. 448,P〈0. 001） ,and it was higher in cases of lymph node metastasis than those without metastasis （0.57±0.06 vs 0. 44±0.05;t=2. 234,P=0. 039）. AOD value of TFF3 was higher in stage Ⅲ-Ⅳ than those in stageⅠ/Ⅱ （0.59±0.07 vs 0. 47 ± 0.05 ; t = 2. 167, P = 0. 041 ）. The positive rate of SDF-1 protein in PTC was higher than that in para-carcinoma tissues （87.10 % vs 16.13 % ;X2 = 31.26, P〈0. 001）, in cases of lymph node metastasis was higher than that without metastasis（100.00% vs 75.00% x2 =4. 306,P=0. 041） ,it was higher in stageⅢ-Ⅳ than stageⅠ/Ⅱ（100.00% vs 63.64%;3（2 =8.35,P=0.04）,it was higher in age over 45 years old than that under 45 （100.00% vs 63.64% x2 =8. 35,P=0. 04）. AOD values of SDF-1 protein in PTC was higher than that in para-carcinoma （0.59±0.07 vs 0. 28±0.08±0. 087,P〈0. 001 7） ,in cases of lymph node metastasis was higher than that without metastasis（0.65±0.06 vs 0.52±0. 05;t=2.458,P=0. 009）,in stage Ⅲ-Ⅳ was higher than that in stageⅠ/Ⅱ （0.66± 0.06 vs 0. 50±0.05;t=2. 762,P=0. 006）. ISH showed that the expression rate of TFF3 and SDF-1 mRNA were consistent with the expression of their proteins. Although the positive rate of TFF3 and SDF-1 mRNA was lower than that of the proteins, it was higher in PTC than in para-carcinoma tissues（x2= 19.37, P〈0. 001 x2 = 26.35, P〈0. 001）. There existed a positive relationship between TFF3 and SDF-1 protein （r=0. 971 ,P=0. 004）. Thirty-one cases of PTC can be divided into three pathological subtypes： 21 cases of typical subtype （67.74%）, 7 cases of follicular subtype （22.58%） and 3 cases of tall cell subtype （9.68 % ）. The positive rate of SDF-1 and TFF3 protein were 86.96 %, 86.96 %, 85.71% and 71.43% ,both 100.00% in typical type, follicular type and tall cell type in turn. There was no statistical significance among different pathological Subtypes. The positive rate of SDF1 in subtype of follicular and tall cell subtype of stage Ⅰ/Ⅱ was higher than that in typical subtype（83.33% and 100.00% vs 0;x2=5.63,P= 0.025;x2=5.00,P=0.046）.The positive rate of TFF3 in tall cell subtype of stage Ⅰ/Ⅱ was higher than that in typical subtype（100.00% vs 0;x2 =5.00, P=0. 046）. The positive rate of TFF3 and SDF-1 in three pathological subtypes of stage Ⅲ-Ⅳ was all 100% ,there was no statistical significance. CONCLUSIONS： The high expression of TFF3 and SDF-1 in PTC were closely correlated with carcinogenesis and progression, and may play a significanct value in judging the malignant degree and progression of PTC. And it may have guiding value in the diagnosis of follicular subtype and tall cell subtype PTC.