雌激素受体β1亚型表达与甲状腺肿瘤微血管密度的相关性及其意义

摘要

目的 探讨雌激素受体β1(ERβ1)在不同组织类型甲状腺癌组织中的表达差异,分析ERβ1表达与肿瘤组织微血管密度(MVD)的相关性.方法 研究样本取自2004年1月-2009年12月临床资料完整的存档标本163例,其中滤泡源性分化型甲状腺癌107例,包括乳头状腺癌(PTC)59例和滤泡状腺癌(FTC)48例;甲状腺腺瘤56例.另取腺瘤旁经病理证实为正常的甲状腺组织10例.采用免疫组化法检测ERβ1和CD31表达,以CD31阳性结果计算组织MVD值.观察不同甲状腺组织中ERβ1和CD31的表达及定位;比较不同病理类型甲状腺癌组织中ERβ1的表达水平,以及甲状腺癌患者颈淋巴结转移与ERβ1表达、MVD的相关性;分析ERβ1.表达与MVD的相关性.结果 CD31主要表达于各种甲状腺组织的血管内皮细胞,ERβ1主要表达于滤泡源性细胞和血管内皮细胞.在正常甲状腺、甲状腺腺瘤和甲状腺癌组织中,ERβ1阳性表达率分别为80.0%、48.2%和29.8%(P<0.05),表达灰度值分别为116.22±14.23、130.08±17.51、146.26±18.13(P<0.05).在甲状腺癌组织中,转移率高、浸润性强的组织类型ERβ1表达较弱,MVD值较高,有淋巴结转移的甲状腺癌组织MVD值显著高于无淋巴结转移者(P<0.05).甲状腺癌ERβ1阳性者的MVD值显著低于ERβ1阴性者(P<0.05),Spearman等级相关分析显示,ERβ1表达与MVD存在显著负相关(r=0.993,P<0.0001).结论 ERβ1表达与甲状腺癌的组织类型、淋巴结转移及MVD有关,ERβ1表达下调可促进甲状腺癌血管生成.%Objective To explore the difference in expression of estrogen receptor beta 1 (ERβ1) in different histological types of thyroid carcinoma, and to investigate the correlation between the ERβ1 expression and microvessel density (MVD) in human thyroid carcinoma tissue. Methods Among 163 paraffin-embedded samples, collected from Jan. 2004 to Dec. 2009, 107 were follicular differentiated thyroid carcinoma [59 cases of papillary thyroid carcinoma (PTC) and 48 cases of follicular thyroid carcinoma (FTC)] , and 56 were thyroid adenoma. Another 10 cases of normal thyroid tissue, pathologically testified, were enrolled as control.Immunohistochemistry was used to evaluate the expressions of ERβ1 and CD31, and the positive results of CD31 were used to calculate MVD of tissues. The expression status and localization of ERβ1 and CD31 in the thyroid tissue were observed, the expression levels of ERβ1 in different histological types of thyroid carcinoma were compared. The correlation between cervical lymph node metastasis of cancer cells and ERβ1 expression and MVD was analyzed, and the correlation between ERβ1 and MVD was also observed. Results CD31 was mainly expressed in vascular endothelial cells in each type of thyroid tissues, while ERβ1 in both follicular epithelial cells and vascular endothelial cells. In different types such as normal thyroid tissue, thyroid adenoma tissue and thyroid carcinoma tissue, the positive expression rate of ERβ1 was 80％, 48.2％ and 29.8％, respectively ( P＜0.05), with mean value of gray level of 116.22±14.23, 130.08 ±17.51, 146.26±18.13, respectively ( P＜0.05). The expression level of ERβ1 was significantly lower in the cancer cells with higher metastasis and strong infiltration than in those with lower metastasis and weaker infiltration ( P＜0.05),and MVD was significant higher in thyroid carcinoma with lymph node metastasis than in those without lymph node metastasis. MVD was notablely lower in thyroid carcinoma tissue with ERβ1 expression than in those without ERβ1 expression. Spearman rank correlation analysis revealed a remarkable reverse correlation between ERβ1 expression and MVD value ( r=-0.993, P＜0.0001) . Conclusion Down regulation of ERβ1 expression may promote angiogenesis and it is associated with histological type, lymph node metastasis and MVD in thyroid carcinoma.