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甲状腺癌中半乳糖凝集素-3的细胞核、细胞质表达与β-连环蛋白/Wnt信号通路激活的相关性

Association of nuclear, cytoplasmic expression of galectin-3 with beta-catenin/Wnt-pathway activation in thyroid carcinoma.

作者信息

Weinberger Paul M, Adam Bao-Ling, Gourin Christine G, Moretz William H, Bollag Roni J, Wang Beverly Y, Liu Zhongmin, Lee Jeffrey R, Terris David J

机构信息

Department of Otolaryngology, Medical College of Georgia, Augusta, GA 30912, USA.

出版信息

Arch Otolaryngol Head Neck Surg. 2007 May;133(5):503-10. doi: 10.1001/archotol.133.5.503.

Abstract

OBJECTIVES

To characterize the localization of galectin-3 in benign and malignant thyroid neoplasms and to correlate this with alterations in beta-catenin and cyclin D1 expression.

DESIGN

Immunohistochemical study of 116 paraffin-embedded archival specimens from 113 patients who had undergone thyroidectomy and tissue placed into a commercially available tissue microarray.

SETTING

Tertiary care hospital.

INTERVENTIONS

Thyroid tissue microarrays were stained by standard immunohistochemical protocols with monoclonal antibodies against galectin-3, beta-catenin, and cyclin D1.

MAIN OUTCOME MEASURES

Nuclear and cytoplasmic expression of galectin-3 was correlated with clinical parameters, beta-catenin, and cyclin D1 expression.

RESULTS

Both cytoplasmic (56%) and nuclear (42%) galectin-3 expression was observed in most malignant neoplasms but was absent in benign thyroid specimens (P<.001). Among carcinomas, cytoplasmic galectin-3 expression was observed in papillary thyroid carcinomas (82%) and follicular (33%) and medullary (9%) carcinomas but was absent in anaplastic carcinomas (P<.001). Galectin-3 nuclear expression was observed in papillary thyroid carcinomas (62%) and follicular carcinomas (33%) but was undetectable in medullary, anaplastic carcinomas (P<.001). Cytoplasmic but not nuclear galectin-3 was inversely correlated with American Joint Committee on Cancer TNM stage (P = .02). There was a strong correlation between cytoplasmic and nuclear beta-catenin expression and both nuclear (P = .04) and cytoplasmic (P = .003) galectin-3 expression. Similarly, there was a strong association between galectin-3 nuclear (P<.001) and cytoplasmic (P<.001) expression and cyclin D1 expression.

CONCLUSION

Cytoplasmic and nuclear galectin-3 expression seem to be associated with activation of the Wnt-signaling pathway in well-differentiated thyroid neoplasms, suggesting that galectin-3 plays a role in thyroid carcinogenesis.

摘要

目的

明确半乳糖凝集素-3在甲状腺良恶性肿瘤中的定位,并将其与β-连环蛋白和细胞周期蛋白D1表达的改变相关联。

设计

对113例行甲状腺切除术患者的116份石蜡包埋存档标本进行免疫组织化学研究,并将组织制成市售组织芯片。

地点

三级医疗中心。

干预措施

采用标准免疫组织化学方法,用抗半乳糖凝集素-3、β-连环蛋白和细胞周期蛋白D1的单克隆抗体对甲状腺组织芯片进行染色。

主要观察指标

半乳糖凝集素-3的核表达和胞质表达与临床参数、β-连环蛋白和细胞周期蛋白D1表达的相关性。

结果

多数恶性肿瘤中均观察到胞质(56%)和核(42%)半乳糖凝集素-3表达,而良性甲状腺标本中未观察到(P<0.001)。在癌组织中,甲状腺乳头状癌(82%)、滤泡状癌(33%)和髓样癌(9%)中观察到胞质半乳糖凝集素-3表达,而未分化癌中未观察到(P<0.001)。甲状腺乳头状癌(62%)和滤泡状癌(33%)中观察到半乳糖凝集素-3核表达,而髓样癌和未分化癌中未检测到(P<0.001)。胞质而非核半乳糖凝集素-3与美国癌症联合委员会TNM分期呈负相关(P = 0.02)。胞质和核β-连环蛋白表达与核(P = 0.04)和胞质(P = 0.003)半乳糖凝集素-3表达均呈强相关。同样,半乳糖凝集素-3核(P<0.001)和胞质(P<0.001)表达与细胞周期蛋白D1表达也呈强相关。

结论

在分化良好的甲状腺肿瘤中,胞质和核半乳糖凝集素-3表达似乎与Wnt信号通路的激活相关,提示半乳糖凝集素-3在甲状腺癌发生中起作用。

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