Choi Sarah M, Furth Emma E, Zhang Paul J
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.
Appl Immunohistochem Mol Morphol. 2016 Sep;24(8):603-7. doi: 10.1097/PAI.0000000000000244.
Thyroid transcription factor-1 (TTF-1) is traditionally used to identify tumors of lung and thyroid primary. However, the specificity of this marker has recently come under increasing scrutiny as tumors from other organ systems are shown to also stain positively for TTF-1. On the basis of an index case of TTF-1-positive gastric adenocarcinomas, we evaluated a retrospective cohort (n=91) of these tumors for TTF-1 staining. Archived paraffin-embedded blocks of gastric adenocarcinoma cases from 2008 to 2013 were chosen for immunohistochemical staining. We report unexpected TTF-1 positivity in up to 25% of cases using the most sensitive TTF-1 clone SPT24. A subset of these cases also shows concurrent Napsin A positivity, including a case with lymph node metastasis, highlighting the potential for diagnostic confusion when dealing with metastatic disease of unknown origin. Because TTF-1 is not detected in the vast majority of cases using a separate antibody clone, 8G7G3/1, we conclude that aberrant staining is due to cross-reactivity to unknown antigen(s). TTF-1 positivity and even Napsin A positivity, therefore, cannot be used as conclusive evidence of pulmonary origin and gastrointestinal origin must be considered in the differential diagnosis.
甲状腺转录因子-1（TTF-1）传统上用于鉴别肺和甲状腺原发性肿瘤。然而，随着来自其他器官系统的肿瘤也被证明TTF-1染色呈阳性，该标志物的特异性最近受到越来越多的审视。基于一例TTF-1阳性胃腺癌的索引病例，我们对一组回顾性队列（n = 91）的此类肿瘤进行了TTF-1染色评估。选取了2008年至2013年胃腺癌病例的存档石蜡包埋块进行免疫组织化学染色。我们报告，使用最敏感的TTF-1克隆SPT24时，高达25%的病例出现意外的TTF-1阳性。这些病例中的一部分还同时显示Napsin A阳性，包括一例有淋巴结转移的病例，这突出了在处理不明来源的转移性疾病时诊断混淆的可能性。由于使用另一种抗体克隆8G7G3/1在绝大多数病例中未检测到TTF-1，我们得出结论，异常染色是由于与未知抗原的交叉反应。因此，TTF-1阳性甚至Napsin A阳性不能用作肺源性的确凿证据，在鉴别诊断中必须考虑胃肠道来源。
