Nonaka Daisuke, Tang Yunjia, Chiriboga Luis, Rivera Michael, Ghossein Ronald
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Mod Pathol. 2008 Feb;21(2):192-200. doi: 10.1038/modpathol.3801002. Epub 2007 Dec 14.
Thyroid-specific transcription factors, Pax8, TTF-1, and TTF-2, are crucial for thyroid organogenesis and differentiation. Compared with TTF-1, the other two markers have scarcely been investigated in surgical pathology. The goal of this study is to evaluate the expressions of these markers in thyroid tumors of the full spectrum of differentiation, with special emphasis on anaplastic carcinomas. A total of 94 cases of thyroid neoplasms were studied: 17 papillary carcinomas, 18 follicular adenomas, 16 follicular carcinomas, 7 poorly differentiated carcinomas, 28 anaplastic carcinomas, and 8 medullary carcinomas. Immunostains for these three markers were performed. The antibodies to Pax8 and TTF-2 were also applied on 147 lung carcinomas as well as a variety of normal tissues and malignant tumors. All three markers were seen in papillary carcinomas, follicular adenomas and carcinomas, and poorly differentiated carcinomas in a diffuse manner, whereas their expressions in medullary carcinomas were variable. Pax8 was expressed in 79% of anaplastic carcinomas to a variable extent, whereas TTF-1 and TTF-2 were seen only in 18 and 7% of anaplastic carcinomas, respectively. TTF-2 was negative in all other neoplastic and non-neoplastic tissues including those of the lung. Pax8 was expressed in renal tubules, fallopian tubes, ovarian inclusion cysts, and lymphoid follicles as well as renal carcinoma, nephroblastoma, seminoma, and ovarian carcinoma, but not in normal tissue and carcinomas of the lung. Pax8 is a useful marker for the diagnosis of anaplastic carcinomas, particularly when the differential diagnosis includes pulmonary carcinoma. In differentiated thyroid neoplasms, no significant difference in expression was seen in all the three transcription factors.
甲状腺特异性转录因子Pax8、TTF-1和TTF-2对甲状腺器官发生和分化至关重要。与TTF-1相比,其他两个标志物在外科病理学中几乎未被研究。本研究的目的是评估这些标志物在全谱分化的甲状腺肿瘤中的表达,特别着重于间变性癌。共研究了94例甲状腺肿瘤:17例乳头状癌、18例滤泡性腺瘤、16例滤泡性癌、7例低分化癌、28例间变性癌和8例髓样癌。对这三种标志物进行了免疫染色。针对Pax8和TTF-2的抗体也应用于147例肺癌以及各种正常组织和恶性肿瘤。在乳头状癌、滤泡性腺瘤和癌以及低分化癌中均可见到所有三种标志物弥漫性表达,而它们在髓样癌中的表达则各不相同。79%的间变性癌不同程度地表达Pax8,而TTF-1和TTF-2分别仅见于18%和7%的间变性癌。TTF-2在所有其他肿瘤性和非肿瘤性组织包括肺组织中均为阴性。Pax8在肾小管、输卵管、卵巢包涵囊肿和淋巴滤泡以及肾癌、肾母细胞瘤、精原细胞瘤和卵巢癌中表达,但在正常组织和肺癌中不表达。Pax8是诊断间变性癌的有用标志物,尤其是在鉴别诊断包括肺癌时。在分化型甲状腺肿瘤中,所有三种转录因子的表达均无显著差异。