TTF1 expression in normal lung neuroendocrine cells and related tumors: immunohistochemical study comparing two different monoclonal antibodies
TTF1 expression in normal lung neuroendocrine cells and related tumors: immunohistochemical study comparing two different monoclonal antibodies
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DOI：
10.1007/s00428-010-0954-0
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发表时间：
2010-10-01
期刊：
影响因子：
3.5
通讯作者：
Capella, Carlo
中科院分区：
文献类型：
--
作者：
La Rosa, Stefano;Chiaravalli, Anna Maria;Capella, Carlo
甲状腺转录因子-1(TTF1)调节肺的形态发生和分化，其免疫组织化学表达用于识别肺肿瘤。8G7G3/1抗体已经在之前的研究中使用过，但一种不同的、更敏感的抗TTF1抗体SPT24已经上市。由于TTF1在正常肺神经内分泌(NE)细胞中的免疫组织化学表达尚未见报道，且其在肺NE肿瘤诊断中的价值尚存争议，因此我们用这两种抗体研究了TTF1在正常成人肺和胎肺、83例肺NE肿瘤、131例非肺NE肿瘤和36例肺转移瘤中的表达。当使用SPT24克隆时，在正常胎儿和成人NE细胞中显示TTF1免疫反应。相反，使用8G7G3/1抗体，只有罕见的胎儿神经内分泌细胞TTF1阳性，而成人NE细胞阴性。与8G7G3/1克隆相比，SPT24克隆在更多的类癌和低分化的NE癌中发现了TTF1的表达，其中大多数位于周边。非肺高分化NE肿瘤两种抗体均为阴性。45例非肺低分化NE癌中，8G7G3/1阳性率为11%，SPT24阳性率为18%。TTF1在转移性肿瘤中的表达较好地反映了相关原发肿瘤的表达。我们的结果表明，SPT24抗体比8G7G3/1克隆更敏感地标记肺癌，在检测周围性肿瘤方面似乎特别有用。此外，TTF1在正常NE细胞中的表达提示转录因子可能在NE细胞的发育和分化中发挥作用。
Thyroid transcription factor-1 (TTF1) regulates lung morphogenesis and differentiation, and its immunohistochemical expression is used for identifying lung neoplasms. The 8G7G3/1 antibody has been used in previous studies, but a different and more sensitive anti-TTF1 antibody, named SPT24, has become commercially available. Since the immunohistochemical expression of TTF1 in normal lung neuroendocrine (NE) cells has not been previously investigated and its utility in the diagnosis of lung NE tumors is a controversial issue, we studied the TTF1 expression in normal adult and fetal lungs, in 83 pulmonary NE neoplasms, in 131 non-lung NE tumors and in 36 metastases from these neoplasms using these two antibodies. A TTF1 immunoreactivity was demonstrated in normal fetal and adult NE cells when using the SPT24 clone. Conversely, using the 8G7G3/1 antibody, only rare fetal neuroendocrine cells were TTF1 positive while adult NE cells were negative. The SPT24 clone identified TTF1 expression in more carcinoids, most of them peripherally located, and poorly differentiated NE carcinomas than the 8G7G3/1 clone. Non-pulmonary well-differentiated NE tumors were negative for both antibodies. Among the 45 non-pulmonary poorly differentiated NE carcinomas 11% were positive for 8G7G3/1 and 18% for SPT24. TTF1 expression in metastases perfectly reflected that detected in the related primary tumors. Our results indicate that the SPT24 antibody is more sensitive than the 8G7G3/1 clone for labeling lung carcinoids and it appears particularly useful in detecting peripheral neoplasms. In addition, the expression of TTF1 in normal NE cells suggests a possible role for the transcription factor in their development and differentiation.