Tzelepi Vassiliki N, Tsamandas Athanassios C, Vlotinou Helen D, Vagianos Constantine E, Scopa Chrisoula D
Faculty of Medicine, Department of Pathology, University Hospital, University of Patras, Patras, Greece.
Mod Pathol. 2008 Jan;21(1):22-30. doi: 10.1038/modpathol.3800959. Epub 2007 Oct 26.
Claudins and occludin are integral constituents of tight junctions and are deregulated in a variety of malignancies. Their role in thyroid carcinogenesis has not yet been elucidated. This study investigates the expression of occludin and claudin-1, -4 and -7 in thyroid neoplasms. Ninety-one thyroid neoplasms (15 follicular adenomas, 15 follicular carcinomas, 26 papillary carcinomas, 16 papillary microcarcinomas, 8 medullary carcinomas, 3 poorly differentiated carcinomas, 8 undifferentiated carcinomas) were immunostained with antibodies against occludin and claudin-1, -4 and -7. Occludin was mainly expressed in the form of intracytoplasmic vesicles, whereas all claudins tested exhibited membranous immunostaining. Thirteen out of 15 follicular adenomas, 10/15 follicular carcinomas, 24/26 papillary carcinomas, 15/16 papillary microcarcinomas, 1/8 medullary carcinomas, 2/3 poorly differentiated carcinomas and 2/8 undifferentiated carcinomas exhibited claudin-1 expression, whereas claudin-4 was expressed in 13/15, 12/15, 23/26, 13/16, 7/8, 2/3 and 2/8 of the tumors, respectively, and claudin-7 expression was found in 67, 33, 73, 69, 25, 0 and 13% of the cases, respectively. Occludin was expressed in 100% follicular adenomas, 80% follicular carcinomas, 96% papillary carcinomas, 50% papillary microcarcinomas, 50% medullary carcinomas, 33% poorly differentiated carcinomas and 88% undifferentiated carcinomas. Occludin expression was reduced in papillary microcarcinomas, medullary carcinomas and poorly differentiated carcinomas. All claudins exhibited reduced expression in undifferentiated carcinomas. Claudin-1 was additionally reduced in medullary carcinomas and claudin-7 in follicular, medullary and poorly differentiated carcinomas. A correlation between loss of claudin-1 expression and worse disease-free survival was noted on univariate analysis. Dedifferentiation of the thyroid carcinomas is accompanied by reduction in claudin-1, -4 and -7 expression. A differential expression of tight junction proteins in the different histologic types of thyroid gland is noted. Additionally, claudin-1 expression may be an important prognostic indicator of recurrence in thyroid carcinomas.
闭合蛋白和咬合蛋白是紧密连接的重要组成部分，在多种恶性肿瘤中表达失调。它们在甲状腺癌发生中的作用尚未阐明。本研究调查了咬合蛋白和闭合蛋白-1、-4及-7在甲状腺肿瘤中的表达情况。对91例甲状腺肿瘤（15例滤泡性腺瘤、15例滤泡性癌、26例乳头状癌、16例微小乳头状癌、8例髓样癌、3例低分化癌、8例未分化癌）用抗咬合蛋白和闭合蛋白-1、-4及-7的抗体进行免疫染色。咬合蛋白主要以胞浆内小泡的形式表达，而所有检测的闭合蛋白均表现为膜性免疫染色。15例滤泡性腺瘤中有13例、15例滤泡性癌中有10例、26例乳头状癌中有24例、16例微小乳头状癌中有15例、8例髓样癌中有1例、3例低分化癌中有2例、8例未分化癌中有2例表达闭合蛋白-1，而闭合蛋白-4分别在13/15、12/15、23/26、13/16、7/8、2/3和2/8的肿瘤中表达，闭合蛋白-7的表达分别见于67%、33%、73%、69%、25%、0和13%的病例。咬合蛋白在100%的滤泡性腺瘤、80%的滤泡性癌、96%的乳头状癌、50%的微小乳头状癌、50%的髓样癌、33%的低分化癌和88%的未分化癌中表达。咬合蛋白在微小乳头状癌、髓样癌和低分化癌中的表达降低。所有闭合蛋白在未分化癌中的表达均降低。闭合蛋白-1在髓样癌中表达额外降低，闭合蛋白-7在滤泡性癌、髓样癌和低分化癌中表达降低。单因素分析显示闭合蛋白-1表达缺失与无病生存期较差相关。甲状腺癌的去分化伴随着闭合蛋白-1、-4和-7表达的降低。注意到紧密连接蛋白在不同组织学类型的甲状腺中存在差异表达。此外，闭合蛋白-1表达可能是甲状腺癌复发的一个重要预后指标。
