Gastrointestinal Pathobiology Research Group, Department of Gastroenterological Surgery, Yale University School of Medicine, New Haven, CT, USA.
Langenbecks Arch Surg. 2011 Mar;396(3):273-98. doi: 10.1007/s00423-011-0739-1. Epub 2011 Jan 28.
Recent data demonstrate that the incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has increased exponentially (overall ~500%) over the last three decades, thus refuting the erroneous concept of rarity. GEP-NETs comprise 2% of all malignancies and in terms of prevalence, are the second commonest gastrointestinal malignancy after colorectal cancer. Diagnosis is usually late since there is no biochemical screening test and symptoms are protean and overlooked. As a consequence, 60-80% exhibit metastases with a consequent suboptimal outcome.
The gastrointestinal tract and pancreas exhibit ~17 different neuroendocrine cell types, but neither the cell of origin nor the biological basis of GEP-NETs is understood. This review examines GEP-NETs from the cellular and molecular perspective and addresses the distinct patterns of functional tumor biology pertinent to clinicians. Although grouped as a neoplastic entity (NETs), each lesion is derived from distinct cell precursors, produces specific bioactive products, exhibits distinct chromosomal abnormalities and somatic mutation events and has uniquely dissimilar clinical presentations. GEP-NETs demonstrate very different survival rates reflecting the intrinsic differences in malignant potential and variations in proliferative regulation. Apart from the identification of the inhibitory role of the somatostatin receptors, there is limited biological knowledge of the key regulators of proliferation and hence a paucity of successful targeted therapeutic agents. IGF-I, TGFβ and a variety of tyrosine kinases have been postulated as key regulatory elements; rigorous data is still required to define predictably effective and rational therapeutic strategy in an individual tumor. A critical issue in the clinical management of GEP-NETs is the need to appreciate both the neuroendocrine commonalities of the disease as well as the unique characteristics of each tumor. The further acquisition of a detailed biological and molecular appreciation of GEP-NETs is vital to the development of effective management strategy.
最近的数据表明，胃肠胰神经内分泌肿瘤（GEP-NETs）的发病率在过去三十年中呈指数级增长（总体约为 500%），从而否定了罕见的错误概念。GEP-NETs 占所有恶性肿瘤的 2%，就患病率而言，是继结直肠癌之后第二常见的胃肠道恶性肿瘤。由于没有生化筛查试验，且症状多样且易被忽视，因此诊断通常较晚。结果，60-80%的患者出现转移，导致治疗效果不佳。
胃肠道和胰腺表现出约 17 种不同的神经内分泌细胞类型，但 GEP-NETs 的起源细胞和生物学基础尚不清楚。本综述从细胞和分子角度探讨了 GEP-NETs，并讨论了与临床医生相关的独特功能性肿瘤生物学模式。尽管被归为肿瘤实体（NETs），但每个病变都源自不同的细胞前体，产生特定的生物活性产物，表现出不同的染色体异常和体细胞突变事件，并且具有独特的临床表现。GEP-NETs 的生存率差异很大，反映了恶性潜能的内在差异和增殖调节的变化。除了鉴定生长抑素受体的抑制作用外，对于增殖的关键调节因子的生物学知识有限，因此缺乏成功的靶向治疗药物。IGF-I、TGFβ 和各种酪氨酸激酶被认为是关键调节因子；仍需要严格的数据来定义个体肿瘤中可预测的有效和合理的治疗策略。在 GEP-NETs 的临床管理中，一个关键问题是需要既了解该疾病的神经内分泌共性，又了解每个肿瘤的独特特征。进一步深入了解 GEP-NETs 的生物学和分子特征对于制定有效的管理策略至关重要。
