Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases
Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases
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DOI：
10.1016/j.prp.2019.152697
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发表时间：
2019-01-01
影响因子：
2.8
通讯作者：
Jung, Loan
中科院分区：
文献类型：
--
作者：
Gurzu, Simons;Fetyko, Annamaria;Jung, Loan
背景：混合性腺神经内分泌癌（MANEC）目前被纳入神经内分泌癌的范畴，但治疗管理尚未明确。目的：观察MANEC上皮间充质转化（epithelial mesenchymal transition， EMT）的免疫组化特征。材料与方法：连续13例MANEC（6例胃，7例结直肠）的临床病理特征与IHC生物标志物E-cadherin、β -catenin、N-cadherin、vimentin、maspin、CD44和S100的表达相关。所有病例均行开腹手术。结果：所有病例均呈微卫星稳定状态，神经内分泌和腺癌两组分均表达E-cadherin和膜β -catenin， N-cadherin、vimentin和S-100均阴性。结直肠manec为阴性。在胃MANECs中，massin在神经内分泌成分中呈细胞质阳性，在腺癌细胞中呈核易位。在所有病例中，CD44在两种成分中都是阳性的。未发现肿瘤萌芽。13例患者中有3例存活至少32个月，均出现淋巴栓塞，但未出现淋巴结转移。单纯的神经内分泌淋巴结转移仅见于4例：1例来自胃，2例来自升结肠，2例来自上直肠。结论：胃肠道MANEC是一种具有结节生长的微卫星稳定肿瘤，其成分可能来源于cd44阳性的干细胞样前体细胞。淋巴结状态仍然是最可靠的预后参数，侵袭性似乎不受肿瘤出芽程度或emt相关特征的影响。转移成分的组织学方面（神经内分泌与腺癌）应包括在组织病理学报告中，并可能用于建立MANEC的适当靶向治疗。
Background: Mixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined.Aims: To present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC.Materials and methods: The clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, beta-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed.Results: All of the cases showed microsatellite stable status, expressed E-cadherin and membrane beta-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum.Conclusions: Gastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.