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目的:分析三叶因子3(trefoil factor 3,TFF3)和基质细胞诱导因子-1(stromal cell derived factor 1,SDF-1)在甲状腺乳头状癌(papillary thyroid carcinoma,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mRNA的表达,以SPSS 18.0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%,χ2=21.10,P<0.001;TFF3阳性率与TNM分期(χ2=12.30,P<0.001)和淋巴结转移(χ2=5.589,P=0.043)有关。PTC内TFF3的平均光密度(average optical density,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%,χ2=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%,χ2=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%,χ2=8.35,P=0.04;>45岁为100.00%,明显高于≤45岁63.64%,χ2=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=0.000 7;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(χ2=19.37,P<0.001),但明显高于癌旁组织,χ2=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PTC 21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),χ2=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),χ2=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),χ2=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。
OBJECTIVE: To investigate the expression of trefoil factor 3 (TFF3) and stromal cell derived factor 1 (SDF-1) in papillary thyroid carcinoma (PTC) and paracancerous tissues Expression and significance, provide valuable information for the early diagnosis and prognosis evaluation of PTC. Methods: Immunohistochemistry and in situ hybridization were used to detect the expression of TFF3 and SDF-1 protein and mRNA in tissue microarray (PTC and adjacent normal tissues). The positive rate and average optical density were analyzed by SPSS 18.0, Characteristics of the relationship. The positive rate of TFF3 protein in PTC was 83.87%, which was significantly higher than that in paracancerous tissue (χ2 = 21.10, P <0.001). The positive rate of TFF3 was positively correlated with TNM stage (χ2 = 12.30, P <0.001) and lymph node metastasis χ2 = 5.589, P = 0.043). The average optical density (AOD) value of TFF3 in PTC was 0.49 ± 0.01, higher than that in adjacent non-cancerous tissues (0.22 ± 0.06, t = 3.448, P <0.001), with lymph node metastasis of 0.57 ± 0.06 (0.44 ± 0.05, t = 2.234, P = 0.039). The clinical stage Ⅲ / Ⅳ was 0.59 ± 0.07, which was higher than that of stage Ⅰ / Ⅱ 0.47 ± 0.05, t = 2.167, P = 0.041.2) The rate was 87.10%, higher than that of paracancerous tissues (16.13%, χ2 = 31.26, P <0.001); those with lymph node metastasis were 100.00%, higher than 75.00% without lymph node metastasis, χ2 = 4.306, The positive rate was 100.00%, which was significantly higher than that of clinical stage Ⅰ / Ⅱ 63.64%, χ2 = 8.35, P = 0.04;> 45 years old was 100.00%, significantly higher than 63.64% ≤45 years old, χ2 = 8.35, P = 0.04. The AOD value of cancerous SDF-1 was 0.59 ± 0.07, which was higher than that of adjacent cancer (0.28 ± 0.08, t = 3.987, P = 0.0007). The positive rate of SDF-1 was 0.65 ± 0.06, which was higher than that of non-lymph node metastasis = 2.458, P = 0.009; the clinical stage Ⅲ / Ⅳ was 0.66 ± 0.06, which was higher than that of stage Ⅰ / Ⅱ 0.50 ± 0.05, t = 2.762, P = 0.006.3) The in situ hybridization showed that the expression of TFF3mRNA and SDF- (Χ2 = 19.37, P <0.001), but it was significantly higher than that in paracancerous tissues (χ2 = 26.35, P <0.001.4). There was a positive correlation between TFF3 and SDF-1 protein expression in PTC, r = 0.971, P = 0.004.5) 31 cases of PTC can be divided into three subtypes: 21 cases of typical PTC (67.74%), 7 cases of follicular type (22.58%) and 3 cases of high cell type (9.68%). The positive rates of SDF-1 and TFF3 protein were typical PTC (86.96% vs 86.96%), follicular PTC (85.71% vs 71.43%) and high cell type PTC (100.00%). The positive rates of SDF-1 and TFF3 The positive rate of SDF-1 in clinical stage Ⅰ / Ⅱ follicles was 83.33%, which was significantly higher than that of typical PTC (0), χ2 = 5.63, P = 0.025. SDF of clinical high cell type PTC 1 positive rate was 100.00%, which was significantly higher than that of typical PTC (0), χ2 = 5.00, P = 0.046. The positive rate of TFF3 (100.00%) in clinical stage Ⅰ / Ⅱ high cell PTC was significantly higher than that of typical PTC (0), χ2 = 5.00, P = 0.046. The positive rates of SDF-1 and TFF3 in three subtypes of clinical stage Ⅲ / Ⅳ were 100.00%, and the difference was not statistically significant. Conclusion: The high expression of TFF3 and SDF-1 in PTC tissues is related to the carcinogenesis and development of PTC, which is of great value in judging the malignancy and progression of PTC. The diagnosis of type I / II follicular and high cell type PTC Guiding significance.