Ohmoto Akihiro, Rokutan Hirofumi, Yachida Shinichi
Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
Int J Mol Sci. 2017 Jan 13;18(1):143. doi: 10.3390/ijms18010143.
Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1%-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC) on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO) classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as , and , whereas NECs have an inactivation of and , and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic background together with preclinical studies to develop new agents, including those already under investigation for small cell lung cancer (SCLC), will be needed to improve the prognosis.
胰腺神经内分泌肿瘤（pNENs）是罕见肿瘤，仅占所有胰腺肿瘤的1%-2%。pNENs在病理上具有异质性，根据2010年世界卫生组织（WHO）胃肠胰神经内分泌肿瘤分类，基于Ki-67增殖指数和有丝分裂计数分为三组（神经内分泌瘤：NET G1、NET G2；神经内分泌癌：NEC）。该分类中的NEC包括组织学高分化和低分化亚型，基于遗传和临床数据，WHO 2010分类的修订正在讨论中。基因组分析显示，NETs G1/G2在染色质重塑基因如 、 和 中存在基因改变，而NECs存在 和 的失活，这些数据表明NET G1/G2和NEC需要不同的治疗方法。虽然对于晚期NET G1/G2有前景良好的分子靶向药物，如依维莫司或舒尼替尼，但基于适当的预测和预后生物标志物进行治疗分层正成为一个重要问题。NEC的临床结局仍然不佳，需要更详细地了解其遗传背景并开展临床前研究以开发新药物，包括那些已在研究用于小细胞肺癌（SCLC）的药物，以改善预后。
