甲状腺癌CCR7和D2-40表达与淋巴结转移的关系
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摘要
目的：研究CCR7及D2-40在甲状腺癌组织中的表达,探讨CCR7及D2-40的表达与淋巴结转移和临床病理特征的关系；为临床治疗、判断淋巴结转移风险提供理论依据；为甲状腺癌靶向治疗提供新思路和方法。方法：1、应用MAX Vision免疫组化法研究趋化因子受体7(CCR7)在87例甲状腺癌和8例正常甲状腺组织中的表达情况。2、应用MAX Vision免疫组化法研究淋巴管内皮标记物D2-40在87例甲状腺癌和8例正常甲状腺组织中的表达情况,光镜下分析观察MLVD并对淋巴管进行定位。3、对甲状腺癌中CCR7及D2-40表达与相关病理因素进行统计分析。结果：1、CCR7标记的棕黄色颗粒主要出现在细胞浆或细胞膜中。87例甲状腺癌CCR7阳性率为66.7%；正常甲状腺组织CCR7阳性率为25%,P=0.019(P<0.05)。2、乳头状癌、髓样癌、滤泡癌、未分化癌CCR7阳性率分别为75.0%、70.0%、73.0%、25.0%,P=0.012(P<0.05)。3、淋巴结阳性组(40/49)与淋巴结阴性组(18/38)CCR7阳性率分别为81.6%；47.4%。卡方检验P=0.001(P<0.05)。4、D2-40主要标记位于甲状腺癌瘤周的淋巴管上皮,而瘤间质内的淋巴管很少表达。87例甲状腺癌和8例正常甲状腺组织中MLVD的计数分别为5.72±2.89；2.60±1.14,甲状腺癌中MLVD归显增高(P<0.05)。5、甲状腺乳头状癌、髓样癌、滤泡癌、未分化癌中MLVD的计数分别为7.55±2.29、6.60±1.75、4.27±1.10、1.00±0.34(P<0.001),有统计学差异。6、甲状腺癌中49例淋巴结阳性组与38例淋巴结阴性组MLVD计数分别为9.39±4.24；3.24±1.67,淋巴结阳性组MLVD计数显著高于淋巴结阴性组(P<0.05)。7、D2-40标记的MLVD与CCR7表达呈正相关(相关系数rs=0.645, p<0.000). CCR7阳性组MLVD (9.37±2.25)高于CCR7阴性组MLVD(5.51±2.47),两者比较具有统计学差异(P<0.05)。8、CCR7及MLVD的表达与年龄、T分期无关,与病理类型和淋巴转移相关。结论：1、D2-40对淋巴管内皮细胞具有敏感性及特异性,能清楚标记出肿瘤淋巴管,区分淋巴管与血管,且肿瘤淋巴管主要分布在瘤周,可应用于肿瘤淋巴管的研究。2、在甲状腺癌中,CCR7阳性率与D2-40标记的MLVD高于正常甲状腺组织。3、甲状腺癌病理类型中,CCR7阳性率与D2-40标记的MLVD有明显区别,表达率分别为乳头状癌>滤泡癌、髓样癌>未分化癌。4、CCR7、MLVD与淋巴结转移呈正相关,甲状腺癌中淋巴结转移阳性组CCR7、MLVD高于甲状腺癌中淋巴结转移阴性组。5、甲状腺癌中CCR7的表达与MLVD呈正相关,CCR7阳性组MLVD高于CCR7阴性组。6、甲状腺癌中MLVD和CCR7与年龄、T分期无关,与病理类型、淋巴结转移有关。在甲状腺癌中,淋巴结转移阳性组CCR7高表达,与D2-40标记的MLVD呈正相关,D2-40仅表达于淋巴淋内皮细胞,肿瘤细胞表达CCR7,联合监测CCR7与D2-40有望成为判断淋巴转移更为有效的指标,并可能为今后治疗甲状腺癌及淋巴转移提供一定的理论依据。
Objectives:To research the expression of the CCR7and D2-40in the thyroid carcinomas tissues; To explore the expression of the CCR7and D2-40in the thyroid carcinomas and the lymph node metastasis along with its characteristics of clinical pathology; To provide some theoretical bases for the clinical diagnosis and the treatment of TC and estimating the risk of lymphatic metastasis; to search a new target and to provide new ideas and methods which may be used to treat thyroid carcinomas.
Methods:1) By means of application of the MAX Vision immunohistochemical staining technique, the expression of the CCR7was measured in the87cases thyroid carcinomas and8cases of thyroid tissues.2) Via application of the MAX Vision immunohistochemical staining technique, the expression of the lymphatic endothelial markers—2-40was measured in the87cases thyroid carcitarnomas and8cases of thyroid tissues,analysede and observed and located the lymphatic vessels in the light microscope.3) To proceed statistic analysis about the expression of the CCR-7and the D2-40in the thyroid carcinomas tissues and the related clinical pathological factors.
Results:1、Pale brown Particles marked by CCR7were seen in the Cell plasma and cell membrane. CCR7was66.7%positive (86/104)in the87cases the thyroid carcinomas and CCR7was25%positive (2/8) in the8cases normal thyroid tissues, P=0.019(P<0.05).2、The CCR7positive rate of the PTC, MTC, FTC, UTC were counted up to75.0%,70.0%,73.0%,25.0%, P=0.012(P<0.05).3、The CCR7was81.6%positive (40/49)in the49cases lymph node metastasis positive patients and47.4%positive (18/38)in the38cases lymph node metastasis negative patients, P=0.000(P<0.05).4、The lymphatic vessels marked by D2-40were rarely seen in the intratumoral tissues of the thyroid carcinomas. The lymphatic vessels mainly distributed in the peritumoral tissues the thyroid carcinomas. The MLVD counts of the thyroid carcinomas and the normal tissues are5.72±2.89;2.60±1.14,The MLVD counts of the thyroid carcinomas obviously more than that of the normal thyroid tissues (P<0.05).5、The MLVD counts of the PTC, MTC, FTC, UTC are respectively7.55±2.29;6.60±1.75;4.27±1.10;1.00±0.34(P<0.05) It has a statistically significant difference.6、The MLVD counts of the49cases lymph node metastasis positive patients obviously more than that of the38cases lymph node metastasis negative patients (9.39±4.24>3.24±1.67,P<0.05).7、The expression ofthe MLVD marked by D2-40and the CCR7is positively correlated (coefficient of correlation, rs=0.645, P<0.000). The MLVD counts in the group of the CCR7-positive (9.37±2.25) is more than that the group of the CCR7-negtive (5.51±2.47).The difference was of statistical significance(P<0.05).8、 The expression of the MLVD and the CCR7counts nothing to do with these factors:age,T-stage. They are connected with lymph node metastasis and Pathological type.
Conclusion:1、The D2-40has specificity and sensitivity to lymphatic endothelial cells, and it can make a distinction between lymphatic vessels and vascular vessels, and can mark clearly tumor lymphatic vessels. The tumor lymphatic vessels mainly distributed in the peritumoral tissues of the thyroid carcinomas, which can apply to research about the tumor lymphatic vessels.2、The positive rate of CCR7and the MLVD marked by D2-40in the TC are more than the group of the normal thyroid tissues.3、In the thyroid carcinomas, It is different of the positive rate of CCR7and the MLVD marked by D2-40,PTC>MTC、FTC>UTC.4、The CCR7and the MLVD are positively relately with lymphatic metastasis, In the TC, The positive rate of CCR7and the MLVDof the lymph node-positive group is more than that of the lymph node-negative group.5、In the TC, The CCR7and the MLVD is also positively related, The MLVD of the CCR7-positive group is more than that of the CCR7-negative group.6、The CCR7and the MLVD have nothing to do with age, T-stages. They are connected with lymph node metastasis and Pathological type.In the thyroid carcinomas, In the lymph node metastasis positive-group,The expression of the CCR7is positively related to the MLVD marked by D2-40.The D2-40staining only presents in the lymphatic endothelial cells. Cancer cell express CCR7, The detection of CCR7along with the D2-40are expected to as inchoate and more effective signal to judgment lymph node metastases. It might provide strong theoretical bases for the treatment thyroid carcinomas and the lymphatic metastasis.
Objectives:To research the expression of the CCR7and D2-40in the thyroid carcinomas tissues; To explore the expression of the CCR7and D2-40in the thyroid carcinomas and the lymph node metastasis along with its characteristics of clinical pathology; To provide some theoretical bases for the clinical diagnosis and the treatment of TC and estimating the risk of lymphatic metastasis; to search a new target and to provide new ideas and methods which may be used to treat thyroid carcinomas.
Methods:1) By means of application of the MAX Vision immunohistochemical staining technique, the expression of the CCR7was measured in the87cases thyroid carcinomas and8cases of thyroid tissues.2) Via application of the MAX Vision immunohistochemical staining technique, the expression of the lymphatic endothelial markers—2-40was measured in the87cases thyroid carcitarnomas and8cases of thyroid tissues,analysede and observed and located the lymphatic vessels in the light microscope.3) To proceed statistic analysis about the expression of the CCR-7and the D2-40in the thyroid carcinomas tissues and the related clinical pathological factors.
Results:1、Pale brown Particles marked by CCR7were seen in the Cell plasma and cell membrane. CCR7was66.7%positive (86/104)in the87cases the thyroid carcinomas and CCR7was25%positive (2/8) in the8cases normal thyroid tissues, P=0.019(P<0.05).2、The CCR7positive rate of the PTC, MTC, FTC, UTC were counted up to75.0%,70.0%,73.0%,25.0%, P=0.012(P<0.05).3、The CCR7was81.6%positive (40/49)in the49cases lymph node metastasis positive patients and47.4%positive (18/38)in the38cases lymph node metastasis negative patients, P=0.000(P<0.05).4、The lymphatic vessels marked by D2-40were rarely seen in the intratumoral tissues of the thyroid carcinomas. The lymphatic vessels mainly distributed in the peritumoral tissues the thyroid carcinomas. The MLVD counts of the thyroid carcinomas and the normal tissues are5.72±2.89;2.60±1.14,The MLVD counts of the thyroid carcinomas obviously more than that of the normal thyroid tissues (P<0.05).5、The MLVD counts of the PTC, MTC, FTC, UTC are respectively7.55±2.29;6.60±1.75;4.27±1.10;1.00±0.34(P<0.05) It has a statistically significant difference.6、The MLVD counts of the49cases lymph node metastasis positive patients obviously more than that of the38cases lymph node metastasis negative patients (9.39±4.24>3.24±1.67,P<0.05).7、The expression ofthe MLVD marked by D2-40and the CCR7is positively correlated (coefficient of correlation, rs=0.645, P<0.000). The MLVD counts in the group of the CCR7-positive (9.37±2.25) is more than that the group of the CCR7-negtive (5.51±2.47).The difference was of statistical significance(P<0.05).8、 The expression of the MLVD and the CCR7counts nothing to do with these factors:age,T-stage. They are connected with lymph node metastasis and Pathological type.
Conclusion:1、The D2-40has specificity and sensitivity to lymphatic endothelial cells, and it can make a distinction between lymphatic vessels and vascular vessels, and can mark clearly tumor lymphatic vessels. The tumor lymphatic vessels mainly distributed in the peritumoral tissues of the thyroid carcinomas, which can apply to research about the tumor lymphatic vessels.2、The positive rate of CCR7and the MLVD marked by D2-40in the TC are more than the group of the normal thyroid tissues.3、In the thyroid carcinomas, It is different of the positive rate of CCR7and the MLVD marked by D2-40,PTC>MTC、FTC>UTC.4、The CCR7and the MLVD are positively relately with lymphatic metastasis, In the TC, The positive rate of CCR7and the MLVDof the lymph node-positive group is more than that of the lymph node-negative group.5、In the TC, The CCR7and the MLVD is also positively related, The MLVD of the CCR7-positive group is more than that of the CCR7-negative group.6、The CCR7and the MLVD have nothing to do with age, T-stages. They are connected with lymph node metastasis and Pathological type.In the thyroid carcinomas, In the lymph node metastasis positive-group,The expression of the CCR7is positively related to the MLVD marked by D2-40.The D2-40staining only presents in the lymphatic endothelial cells. Cancer cell express CCR7, The detection of CCR7along with the D2-40are expected to as inchoate and more effective signal to judgment lymph node metastases. It might provide strong theoretical bases for the treatment thyroid carcinomas and the lymphatic metastasis.
引文
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