Pathogenic Factors And Determinants Of Prognosis In Pati

最近的研究表明，胃泌素瘤与类癌和除胰岛素瘤外的所有其他胰腺内分泌肿瘤(PET)相似，通常(60%-90%)是恶性的，有些可能具有侵袭性。分子发病机制，不仅对于肿瘤本身，而且对于决定其生长行为几乎完全未知。最近的研究表明，与许多其他更常见的癌症相比，癌基因和常见的抑癌基因(P53、视网膜母细胞瘤、VHL基因等)都不是癌基因。在胃泌素瘤、类癌或其他PET中通常会发生改变。美国国立卫生研究院最近的分析发现，25%的胃泌素瘤患者进行了积极的临床病程。通过统计分析，以及与胃泌素瘤中可能的分子变化的相关性，寻找区分具有侵袭性病程的患者的临床和实验室特征，这可能与预后和肿瘤生长相关。我们最近的研究表明，参与维持细胞周期控制的肿瘤抑制基因p16在胃泌素瘤中经常(50%)发生改变，完全是由于启动子区域富含CG的岛的甲基化所致。此外，在40%的病例中发现了MEN1基因的改变。目前，我们正在研究生长因子(EGFR、HGFR和VEFR)在胃泌素瘤、HER-2/neu癌基因改变和PET第一染色体LOH中的重要性，因为这些改变中的每一个都与许多非内分泌肿瘤的侵袭性生长相关。识别与肿瘤生长相关的分子改变将有助于识别需要更积极治疗的肿瘤患者。

Recent studies demonstrate gastrinomas, similar to carcinoid tumors and all other pancreatic endocrine tumors (PET's) except insulinomas, frequently (60-90%) are malignant and some may have an aggressive course. The molecular pathogenesis, not only for the tumors themselves, but also for determining their growth behavior is almost completely unknown. Recent studies demonstrate that in contrast to many other more common cancers neither oncogenes nor common tumor suppressor genes (p53, retinoblastoma, VHL gene, etc.) are generally altered in gastrinomas, carcinoids or other PET's. Recent analyses at NIH have identified a cohort of 25% of patients in whom gastrinomas pursued an aggressive clinical course. Both clinical and laboratory characteristics that distinguish patients with an aggressive course are being sought by statistical analysis as well as correlations with possible molecular changes in the gastrinoma that may correlate with prognosis and tumor growth. Our recent studies demonstrate that the tumor suppressor gene, p16, which is involved in maintaining cell cycle control, is frequently (50%) altered in gastrinomas, entirely due to methylation of CG-rich islands in the promoter region. Furthermore, alterations are found in the MEN1 gene in 40%. At present we are investigating the importance of overexpression of growth factors (EGFR, HGFR, and VEFR)in gastrinomas, alterations in the HER-2/neu oncogene and LOH in chromosome one in PET's because alterations in each of these correlate with aggressive growth in a number of nonendocrine tumors. The identification of molecular alteration that correlate with tumor growth will allow identification of patients with tumors that warrant more aggressive treatment.