Department of Pathology, Ospedale di Circolo, 21100 Varese, Italy.
Hum Pathol. 2013 Jul;44(7):1391-9. doi: 10.1016/j.humpath.2012.11.013. Epub 2013 Jan 31.
Neuroendocrine carcinomas show overlapping morphological and immunohistochemical features independently of their site of origin, which makes identification of the primary location problematic when they are diagnosed as metastases of unknown origin. Neuroendocrine carcinomas are easily morphologically differentiated from neuroendocrine tumors in surgical material, although this distinction can be difficult when using small biopsy specimens. The diagnostic usefulness of different transcription factors as site-specific markers or as discriminating markers between neuroendocrine carcinomas and neuroendocrine tumors has been previously studied with sometimes contradictory results. In this respect, the role of achaete-scute homolog 1 has been poorly investigated, although some recent findings demonstrate its expression in neuroendocrine carcinomas. Using immunohistochemistry and quantitative real-time polymerase chain reaction, we investigated the expression of achaete-scute homolog 1 in 335 neuroendocrine neoplasms (194 neuroendocrine carcinomas and 141 neuroendocrine tumors) of different sites, to check its possible utility as diagnostic marker. High concordance between immunohistochemical and molecular findings was found. Achaete-scute homolog 1 expression was identified in 82% of lung neuroendocrine carcinomas and 70% of extrapulmonary neuroendocrine carcinomas. Achaete-scute homolog 1 was not detected in any gastroenteropancreatic neuroendocrine tumor and was found in only a minority of lung carcinoids. The diagnostic sensitivity and specificity of achaete-scute homolog 1 expression were 82.4% and 89.7% in distinguishing neuroendocrine carcinomas from neuroendocrine tumors of the lung, 40.6% and 100% to differentiate extrapulmonary neuroendocrine carcinomas from neuroendocrine tumors, and 82.4% and 59.4% in distinguishing lung from extrapulmonary neuroendocrine carcinomas. Our data suggest that achaete-scute homolog 1 is not a site-specific marker. However, achaete-scute homolog 1 may be proposed as a diagnostic marker of poor differentiation and may help to differentiate neuroendocrine carcinomas from neuroendocrine tumors in difficult cases.
神经内分泌癌表现出与起源部位无关的重叠形态学和免疫组织化学特征，这使得当它们被诊断为不明来源的转移瘤时，确定原发部位成为问题。神经内分泌癌在手术标本中很容易与神经内分泌肿瘤在形态学上区分开来，尽管在使用小活检标本时，这种区分可能很困难。以前曾使用不同的转录因子作为特定部位的标志物或作为神经内分泌癌与神经内分泌肿瘤之间的鉴别标志物进行了研究，但结果有时相互矛盾。在这方面，achaete-scute 同源物 1 的作用研究得很少，尽管最近的一些发现表明其在神经内分泌癌中的表达。我们使用免疫组织化学和实时定量聚合酶链反应研究了 335 例不同部位的神经内分泌肿瘤（194 例神经内分泌癌和 141 例神经内分泌肿瘤）中 achaete-scute 同源物 1 的表达，以检查其作为诊断标志物的可能用途。免疫组织化学和分子发现之间存在高度一致性。在 82%的肺神经内分泌癌和 70%的肺外神经内分泌癌中检测到 achaete-scute 同源物 1 的表达。在任何胃肠胰神经内分泌肿瘤中均未检测到 achaete-scute 同源物 1，在少数肺类癌中仅发现少数。在区分肺神经内分泌癌和肺神经内分泌肿瘤时，achaete-scute 同源物 1 表达的诊断敏感性和特异性分别为 82.4%和 89.7%，区分肺外神经内分泌癌和神经内分泌肿瘤的诊断敏感性和特异性分别为 40.6%和 100%，区分肺和肺外神经内分泌癌的诊断敏感性和特异性分别为 82.4%和 59.4%。我们的数据表明，achaete-scute 同源物 1 不是特定部位的标志物。然而，achaete-scute 同源物 1 可以作为低分化的诊断标志物，并有助于在困难情况下区分神经内分泌癌和神经内分泌肿瘤。
