Agoff S N, Lamps L W, Philip A T, Amin M B, Schmidt R A, True L D, Folpe A L
Department of Pathology, University of Washington, Seattle, USA.
Mod Pathol. 2000 Mar;13(3):238-42. doi: 10.1038/modpathol.3880044.
Thyroid transcription factor-1 (TTF-1) is a nuclear homeodomain transcription factor that is expressed in the developing thyroid, respiratory epithelium, and diencephalon. TTF-1 is thought to be expressed specifically in pulmonary or thyroid neoplasms, and it is expressed in a significant subset of pulmonary non-small cell carcinomas, small cell carcinomas, and carcinoids but not in nonpulmonary, non-small cell carcinomas. Neuroendocrine tumors from sites other than the lung have not been evaluated for TFF-1 expression. We examined TFF-1 expression using immunohistochemistry on formalin-fixed, paraffin-embedded sections of 49 gastrointestinal carcinoids; 15 pancreatic islet cell tumors; 21 paragangliomas; 8 medullary thyroid carcinomas; 7 small cell carcinomas of the uterine cervix; 4 prostate, 4 bladder, and 6 Merkel cell (primary cutaneous neuroendocrine) carcinomas; and 1 renal carcinoma No gastrointestinal carcinoid tumor, pancreatic islet cell tumor, paraganglioma, or Merkel cell carcinoma expressed TFF-1. All of the medullary thyroid carcinomas strongly expressed TTF-1. However, 44% of nonpulmonary small cell carcinomas were also TTF-1 positive, including four of four prostate, two of four bladder, and one of seven cervical small cell carcinomas. We conclude that TTF-1 expression is not specific for small cell carcinomas of pulmonary origin and should not be used to distinguish primary from metastatic small cell carcinomas in extrapulmonary sites. However, TTF-1 expression may be useful in distinguishing Merkel cell carcinomas and cutaneous metastasis of small cell carcinomas. Among well-differentiated neuroendocrine tumors, TTF-1 expression seems to be present only in carcinoid tumors of the lung and medullary carcinomas of the thyroid and may be of differential diagnostic value when dealing with a metastatic well-differentiated neuroendocrine tumor.
甲状腺转录因子-1（TTF-1）是一种核内同源异型域转录因子，在发育中的甲状腺、呼吸道上皮和间脑中表达。TTF-1被认为在肺或甲状腺肿瘤中特异性表达，它在相当一部分肺非小细胞癌、小细胞癌和类癌中表达，但在非肺非小细胞癌中不表达。尚未对肺外部位的神经内分泌肿瘤进行TTF-1表达评估。我们采用免疫组化方法检测了49例胃肠道类癌、15例胰岛细胞瘤、21例副神经节瘤、8例甲状腺髓样癌、7例子宫颈小细胞癌、4例前列腺癌、4例膀胱癌、6例默克尔细胞（原发性皮肤神经内分泌）癌和1例肾癌的福尔马林固定石蜡包埋切片中的TTF-1表达。没有胃肠道类癌、胰岛细胞瘤、副神经节瘤或默克尔细胞癌表达TTF-1。所有甲状腺髓样癌均强烈表达TTF-1。然而，44%的非肺小细胞癌TTF-1也呈阳性，包括4例前列腺癌中的4例、4例膀胱癌中的2例和7例宫颈小细胞癌中的1例。我们得出结论，TTF-1表达并非肺源性小细胞癌所特有，不应将其用于区分肺外部位的原发性和转移性小细胞癌。然而，TTF-1表达可能有助于区分默克尔细胞癌和小细胞癌的皮肤转移。在高分化神经内分泌肿瘤中，TTF-1表达似乎仅见于肺类癌和甲状腺髓样癌，在处理转移性高分化神经内分泌肿瘤时可能具有鉴别诊断价值。
