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一种新型肿瘤标志物Niban在甲状腺肿瘤和桥本甲状腺炎的某些亚群中表达。

A novel tumor marker, Niban, is expressed in subsets of thyroid tumors and Hashimoto's thyroiditis.

作者信息

Matsumoto Fumihiko, Fujii Hiroaki, Abe Masaaki, Kajino Kazunori, Kobayashi Toshiyuki, Matsumoto Toshiharu, Ikeda Katsuhisa, Hino Okio

机构信息

Department of Otorhinolaryngology, Juntendo University School of Medicine, Tokyo, Japan.

出版信息

Hum Pathol. 2006 Dec;37(12):1592-600. doi: 10.1016/j.humpath.2006.06.022. Epub 2006 Sep 1.

Abstract

Niban is a recently identified molecular marker of renal carcinogenesis in the Tsc2 gene-mutant Eker rat. Niban expression is most dramatically increased in the early stage of renal carcinogenesis and might decline during malignant progression. Niban is also expressed in various histologic types of human renal cell carcinoma. Therefore, Niban might be a good marker for renal carcinogenesis in both animal models and humans. In the present study, we examined Niban expression in various thyroid lesions by immunohistochemical staining using polyclonal rabbit antihuman Niban antibody. Normal thyroid tissue never stained for Niban. Niban was most frequently expressed in tumors with oxyphilic cytoplasm, including oxyphilic variants of papillary carcinoma (4/4 = 100%), oxyphilic variants of follicular adenoma (7/7 = 100%), and oxyphilic variants of follicular carcinoma (5/5 = 100%). Eighty-one percent (44/54) of papillary carcinoma cases, including microcarcinomas, and follicular variants were also positively stained for Niban at variable intensities. Follicular carcinomas were less frequently and less intensely stained. In nonneoplastic lesions, cells were rarely positively stained. In Hashimoto's thyroiditis, scattered cells with oxyphilic cell metaplasia were weakly Niban-positive. Reverse transcriptase-polymerase chain reaction and Western blot analysis of frozen tissue confirmed Niban expression at the molecular level in 4 cases of papillary carcinoma. Taken together, Niban expression is up-regulated in various types of thyroid tumors. We postulate that Niban expression may play an important role in the tumorigenic process of the thyroid in several scenarios. (1) Niban expression may be closely related to the carcinogenic process, especially from the early stage of papillary thyroid carcinoma. (2) Niban may be closely associated with altered mitochondrial functions in preneoplastic and neoplastic processes of the thyroid. (3) Niban may be a molecular marker of the oxyphilic phenotype under various conditions. Further functional studies of Niban will clarify the role of Niban in various thyroid lesions.

摘要

Niban是最近在Tsc2基因敲除的Eker大鼠肾致癌过程中鉴定出的分子标志物。Niban表达在肾致癌早期显著增加,在恶性进展过程中可能下降。Niban也在各种组织学类型的人类肾细胞癌中表达。因此,Niban可能是动物模型和人类肾致癌的良好标志物。在本研究中,我们使用兔抗人Niban多克隆抗体通过免疫组织化学染色检测了Niban在各种甲状腺病变中的表达。正常甲状腺组织未检测到Niban染色。Niban最常在具有嗜酸性细胞质的肿瘤中表达,包括乳头状癌嗜酸性变体(4/4 = 100%)、滤泡性腺瘤嗜酸性变体(7/7 = 100%)和滤泡癌嗜酸性变体(5/5 = 100%)。81%(44/54)的乳头状癌病例,包括微癌和滤泡变体,也以不同强度对Niban呈阳性染色。滤泡癌染色频率较低且强度较弱。在非肿瘤性病变中,细胞很少呈阳性染色。在桥本甲状腺炎中,散在的具有嗜酸性细胞化生的细胞呈弱阳性Niban染色。对冰冻组织的逆转录聚合酶链反应和蛋白质印迹分析证实了4例乳头状癌在分子水平上的Niban表达。综上所述,Niban表达在各种类型的甲状腺肿瘤中上调。我们推测Niban表达可能在几种情况下在甲状腺的致瘤过程中起重要作用。(1)Niban表达可能与致癌过程密切相关,尤其是从甲状腺乳头状癌的早期阶段开始。(2)Niban可能与甲状腺肿瘤发生前和肿瘤形成过程中线粒体功能的改变密切相关。(3)Niban可能是各种条件下嗜酸性表型的分子标志物。对Niban的进一步功能研究将阐明Niban在各种甲状腺病变中的作用。

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