Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy.
1(st) Division of Pathology, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy.
Cancer Treat Rev. 2016 Nov;50:61-67. doi: 10.1016/j.ctrv.2016.08.006. Epub 2016 Aug 28.
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are currently classified as grade (G) 1, G2 and G3, in accordance with the 2010 WHO classification. G1 and G2 are named neuroendocrine tumors (NETs) whereas G3 neuroendocrine carcinomas (NECs). While advanced G1 and G2 are usually treated with several different therapies, including somatostatin analogs, chemotherapy, interferon, molecular targeted agents, peptide receptor radionuclide therapy (PRRT) and liver-directed treatments, advanced G3 NECs are usually treated with a platinum-etoposide chemotherapy, trusting their clinical homogeneity is similar to that of small cell lung cancer. However, over the last years a number of reports suggested that 2010 WHO G3 GEP NECs are more heterogeneous than expected. Therefore, we critically reviewed the literature about this topic and reported pathological and clinical considerations on 2010 WHO G3 GEP NEC category proposing new sub-categories. Over the last five years, six studies specifically investigating large series of G3 GEP NECs have been published, including around 800 patients. Tumor morphology and Ki-67 Labeling Index (that will be mentioned as Ki-67 in this manuscript) combination has been reported as a tool to define two or even three subgroups of this category with different prognosis and potentially different therapeutic approach. Prospective trials are warranted to investigate if several types of therapy other than the platinum/etoposide chemotherapy can be effective in well differentiated GEP NEN with 21-55% Ki-67 and alkylating-based chemotherapy in poorly differentiated GEP NEN with 21-55% Ki-67.
胃肠胰神经内分泌肿瘤（GEP-NENs）目前根据 2010 年 WHO 分类，分为 G1、G2 和 G3 级。G1 和 G2 称为神经内分泌肿瘤（NETs），而 G3 称为神经内分泌癌（NECs）。虽然高级别 G1 和 G2 通常采用多种不同的治疗方法，包括生长抑素类似物、化疗、干扰素、分子靶向药物、肽受体放射性核素治疗（PRRT）和肝靶向治疗，但高级别 G3 NEC 通常采用铂类依托泊苷化疗，因为人们相信它们的临床同质性与小细胞肺癌相似。然而，近年来有许多报道表明，2010 年 WHO G3 GEP NEC 比预期的更具异质性。因此，我们对这一主题的文献进行了批判性回顾，并报告了关于 2010 年 WHO G3 GEP NEC 类别的病理和临床考虑因素，提出了新的亚类。在过去的五年中，有六项专门研究 G3 GEP NEC 大系列的研究已经发表，包括大约 800 名患者。肿瘤形态和 Ki-67 标记指数（在本手稿中称为 Ki-67）的组合已被报道为定义该类别的两个甚至三个亚组的工具，这些亚组具有不同的预后和潜在的不同治疗方法。需要进行前瞻性试验，以研究除铂类/依托泊苷化疗以外的其他几种类型的治疗方法是否对 Ki-67 为 21-55%的分化良好的 GEP-NEN 和 Ki-67 为 21-55%的低分化 GEP-NEN 具有疗效。
