Srivastava Amitabh, Hornick Jason L
Dartmouth Medical School, Dartmouth-Hitchcock Medical Center Lebanon, NH, USA.
Am J Surg Pathol. 2009 Apr;33(4):626-32. doi: 10.1097/PAS.0b013e31818d7d8b.
Well-differentiated neuroendocrine tumors (WDNET) of the gastrointestinal tract, pancreas, and lung are histologically similar. Thus, predicting the site of origin of a metastasis is not possible on morphologic grounds. Prior immunohistochemical studies of WDNET have yielded conflicting results, and pancreatic and duodenal homeobox factor-1 (PDX-1) has not previously been evaluated in this context. We therefore analyzed the expression of CDX-2, PDX-1, TTF-1, and neuroendocrine secretory protein-55 (NESP-55), a recently described member of the chromogranin family, in primary and metastatic WDNET. In total, 64 gastrointestinal carcinoids (5 stomach; 5 duodenum; 31 ileum; 11 appendix; and 12 rectum); 39 pancreatic endocrine tumors (PET); and 20 pulmonary carcinoid tumors were studied. PET were positive for NESP-55 (16/39) and PDX-1 (11/39); 3/31 also showed heterogeneous positivity for CDX-2. Ileal carcinoids were exclusively positive for CDX-2 (30/31) and negative for all other markers. Appendiceal carcinoids were uniformly positive for CDX-2 (11/11). All rectal carcinoids were negative for CDX-2 and TTF-1; 2/12 were positive for PDX-1, and 1/12 for NESP-55. The gastric and duodenal carcinoids were only positive for PDX-1 (7/10). TTF-1 positivity was confined to pulmonary carcinoids (7/20); 1/20 was positive for NESP-55; and all were negative for CDX-2 and PDX-1. NESP-55 and PDX-1 positivity, in the presence of negative CDX-2 and TTF-1, was 97% specific for PET. The sensitivity and specificity of CDX-2 positivity for predicting an ileal primary, when PDX-1, NESP-55, and TTF-1 were negative, was 97% and 91%, respectively. TTF-1 positivity was confined to pulmonary carcinoids in our study but was present in only about a third of cases. A panel of these 4 markers may be useful in predicting the primary site of metastatic WDNET.
胃肠道、胰腺和肺部的高分化神经内分泌肿瘤（WDNET）在组织学上相似。因此，基于形态学依据无法预测转移灶的起源部位。先前对WDNET的免疫组织化学研究结果相互矛盾，且此前尚未在此背景下评估胰腺和十二指肠同源盒因子-1（PDX-1）。因此，我们分析了尾型同源盒转录因子2（CDX-2）、PDX-1、甲状腺转录因子-1（TTF-1）和嗜铬粒蛋白家族最近描述的成员神经内分泌分泌蛋白-55（NESP-55）在原发性和转移性WDNET中的表达。总共研究了64例胃肠道类癌（5例胃；5例十二指肠；31例回肠；11例阑尾；12例直肠）；39例胰腺内分泌肿瘤（PET）；以及20例肺类癌肿瘤。PET对NESP-55（16/39）和PDX-1（11/39）呈阳性；3/31对CDX-2也显示出异质性阳性。回肠类癌仅对CDX-2呈阳性（30/31），对所有其他标志物呈阴性。阑尾类癌对CDX-2均呈阳性（11/11）。所有直肠类癌对CDX-2和TTF-1均呈阴性；2/12对PDX-1呈阳性，1/12对NESP-55呈阳性。胃和十二指肠类癌仅对PDX-1呈阳性（7/10）。TTF-1阳性仅限于肺类癌（7/20）；1/20对NESP-55呈阳性；所有肺类癌对CDX-2和PDX-1均呈阴性。在CDX-2和TTF-1为阴性的情况下，NESP-55和PDX-1阳性对PET的特异性为97%。当PDX-1、NESP-55和TTF-1为阴性时，CDX-2阳性预测回肠原发性的敏感性和特异性分别为97%和91%。在我们的研究中，TTF-1阳性仅限于肺类癌，但仅约三分之一的病例中存在。这4种标志物的组合可能有助于预测转移性WDNET的原发部位。
