Department of Pathology, University of Washington School of Medicine, Seattle, 98195-6100, USA.
Am J Surg Pathol. 2012 May;36(5):737-43. doi: 10.1097/PAS.0b013e31824aba59.
Neuroendocrine tumors (NETs) occur in virtually all sites of the body. As NETs arising in different organs share similar morphologic features, distinguishing metastatic from primary NETs on the basis of morphologic grounds alone is difficult. Pancreatic duodenal homeobox 1 (PDX-1) is a Hox-type transcription factor that is essential for both exocrine and endocrine pancreatic differentiation and maintenance of β-cell function. We investigated PDX-1 as an immunohistochemical (IHC) marker in primary pancreatic NETs. Eighty primary NETs [25 pancreatic, 29 bronchopulmonary, and 26 in the gastrointestinal (GI) tract] and 13 metastatic NETs in the liver were studied. Clinical and radiologic data were reviewed to confirm the stated primary sites. IHC analysis for PDX-1, CDX-2, thyroid transcription factor-1 (TTF-1), keratin 7 (CK7), and keratin 20 (CK20) was performed, and the results were based on review blinded to the primary sites. PDX-1 was seen in 18 of 25 (72%) pancreatic NETs; in contrast, only 3 of 29 (10%) bronchopulmonary NETs and 1 of 26 (4%) GI NETs were positive. PDX-1 was therefore 93% specific and 72% sensitive for pancreatic NETs. TTF-1 was expressed only in bronchopulmonary NETs; all other NETs were negative for TTF-1. CK7 was also very specific (92%) and moderately sensitive (66%) for bronchopulmonary NETs. CDX-2 was seen in 22 of 26 (85%) cases of GI NETs and in only 1 of 51 (2%) cases of extra-GI NETs. Thus, CDX-2 was 98% specific and 85% sensitive for GI NETs. In terms of metastatic NETs found in the liver, PDX-1 was positive in 5 of 5 cases of metastatic pancreatic NETs and 2 of 2 cases of metastatic duodenal NETs. PDX-1 is highly specific, with very good overall diagnostic accuracy for pancreatic NETs. An IHC panel including PDX-1, CDX-2, TTF-1, CK7, and CK20 may be useful in distinguishing NETs of pancreatic origin from other primaries.
神经内分泌肿瘤（NETs）几乎可发生于全身所有部位。由于不同器官起源的 NETs 具有相似的形态学特征，仅基于形态学基础来区分转移性和原发性 NETs 较为困难。胰腺十二指肠同源盒 1（PDX-1）是一种 Hox 型转录因子，对于外分泌和内分泌胰腺的分化以及β细胞功能的维持都是必需的。我们研究了 PDX-1 作为原发性胰腺 NETs 的免疫组织化学（IHC）标志物。研究了 80 例原发性 NETs[25 例胰腺、29 例支气管肺和 26 例胃肠道（GI）]和 13 例肝转移 NETs。回顾临床和影像学数据以确认所陈述的原发部位。进行了 PDX-1、CDX-2、甲状腺转录因子-1（TTF-1）、角蛋白 7（CK7）和角蛋白 20（CK20）的免疫组化分析，结果基于对原发部位不知情的回顾性审查。PDX-1 在 25 例胰腺 NETs 中的 18 例中呈阳性；相比之下，仅在 29 例支气管肺 NETs 中的 3 例和 26 例 GI NETs 中的 1 例呈阳性。因此，PDX-1 对胰腺 NETs 的特异性为 93%，敏感性为 72%。TTF-1 仅在支气管肺 NETs 中表达；所有其他 NETs 均为 TTF-1 阴性。CK7 对支气管肺 NETs 也具有非常高的特异性（92%）和中等敏感性（66%）。CDX-2 在 26 例 GI NETs 中的 22 例中可见，而在 51 例非 GI NETs 中的 1 例中可见。因此，CDX-2 对 GI NETs 的特异性为 98%，敏感性为 85%。就肝转移 NETs 而言，PDX-1 在 5 例转移性胰腺 NETs 和 2 例转移性十二指肠 NETs 中均为阳性。PDX-1 具有高度特异性，对胰腺 NETs 的总体诊断准确性非常高。包括 PDX-1、CDX-2、TTF-1、CK7 和 CK20 的 IHC 组合可能有助于区分胰腺起源的 NETs 与其他原发性肿瘤。
