胃肠胰腺神经内分泌肿瘤(GEP-NEN),被认为是异质性肿瘤,表现出不明确的病理生物学和蛋白质症状学,并且在位置上无处不在。它们很难诊断,具有挑战性的管理,结果取决于细胞类型,分泌产物,组织病理学分级,和起源器官。对这些病变的形态学和分子基因组回顾突出了可用于临床的肿瘤特征,如生长抑素受体表达,并确认将它们设置在标准瘤形成范式之外的特征。它们独特的病理生物学可用于开发使用生长抑素受体靶向成像或吸收对分泌产物或代谢特异的放射性标记氨基酸的诊断。治疗已通过用药物或同位素靶向蛋白激酶B信号或生长抑素受体(肽受体放射疗法)而发展。有了DNA测序,很少发现的激活突变证实肿瘤抑制基因是相关的.专注于癌症相关基因和信号通路的基因组方法可能仍然没有提供信息。它们独特的不同分子谱意味着个体肿瘤不太可能被目前与标准癌症遗传范例相关的治疗剂容易或均匀地靶向。胰腺NEN中的menin突变和小肠NEN中的P27KIP1突变的患病率代表了鉴定GEP-NEN中调控共性的初始步骤。转录分析和基于网络的分析可以定义细胞工具包。多分析物诊断工具有助于对NEN进行更准确的分子病理学描述,以评估预后并确定个性化患者治疗的策略。GEP-NEN仍然独一无二,了解不足的实体,深入了解他们的病理生物学和生长和转移的分子机制将有助于确定这种肿瘤的诊断和治疗弱点。
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), considered a heterogeneous neoplasia, exhibit ill-defined pathobiology and protean symptomatology and are ubiquitous in location. They are difficult to diagnose, challenging to manage, and outcome depends on cell type, secretory product, histopathologic grading, and organ of origin. A morphologic and molecular genomic review of these lesions highlights tumor characteristics that can be used clinically, such as somatostatin-receptor expression, and confirms features that set them outside the standard neoplasia paradigm. Their unique pathobiology is useful for developing diagnostics using somatostatin-receptor targeted imaging or uptake of radiolabeled amino acids specific to secretory products or metabolism. Therapy has evolved via targeting of protein kinase B signaling or somatostatin receptors with drugs or isotopes (peptide-receptor radiotherapy). With DNA sequencing, rarely identified activating mutations confirm that tumor suppressor genes are relevant. Genomic approaches focusing on cancer-associated genes and signaling pathways likely will remain uninformative. Their uniquely dissimilar molecular profiles mean individual tumors are unlikely to be easily or uniformly targeted by therapeutics currently linked to standard cancer genetic paradigms. The prevalence of menin mutations in pancreatic NEN and P27KIP1 mutations in small intestinal NEN represents initial steps to identifying a regulatory commonality in GEP-NEN. Transcriptional profiling and network-based analyses may define the cellular toolkit. Multianalyte diagnostic tools facilitate more accurate molecular pathologic delineations of NEN for assessing prognosis and identifying strategies for individualized patient treatment. GEP-NEN remain unique, poorly understood entities, and insight into their pathobiology and molecular mechanisms of growth and metastasis will help identify the diagnostic and therapeutic weaknesses of this neoplasia.