Libutti S K, Choyke P L, Alexander H R, Glenn G, Bartlett D L, Zbar B, Lubensky I, McKee S A, Maher E R, Linehan W M, Walther M M
Surgical Metabolism Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Surgery. 2000 Dec;128(6):1022-7;discussion 1027-8. doi: 10.1067/msy.2000.110239.
Patients with von Hippel-Lindau disease (VHL) may develop pancreatic neuroendocrine tumors (PNETs), which can behave in a malignant fashion. We prospectively evaluated size criteria for resection of lesions and the role of genotype/phenotype analysis of germline VHL mutations in predicting clinical course.
From December 1988 through December 1999 we screened 389 patients with VHL. The diagnosis of PNET was made by pathologic analysis of tissues or by radiographic appearance. Germline mutations were determined by quantitative Southern blotting, fluorescence in situ hybridization and complete gene sequencing.
Forty-four patients with PNETs have been identified; 25 have undergone surgical resection, 5 had metastatic disease, and 14 are being monitored. No patient who has undergone resection based on tumor size criteria has developed metastases. Patients with PNETs were more likely to have missense mutations (58%), and 4 of 5 patients (80%) with metastatic disease had mutations in exon 3 compared with 18 of 39 (46%) patients without metastatic disease.
Imaging for detection and surgical resection based on size criteria have resulted in the successful management of VHL patients with PNETs. Analysis of germline mutations may help identify patients at risk for PNET and which patients may benefit from surgical intervention.
冯·希佩尔-林道病（VHL）患者可能会发生胰腺神经内分泌肿瘤（PNET），其可能具有恶性行为。我们前瞻性地评估了病变切除的大小标准以及种系VHL突变的基因型/表型分析在预测临床病程中的作用。
从1988年12月至1999年12月，我们对389例VHL患者进行了筛查。PNET的诊断通过组织病理学分析或影像学表现做出。种系突变通过定量Southern印迹法、荧光原位杂交和全基因测序确定。
已确定44例PNET患者；25例接受了手术切除，5例有转移性疾病，14例正在接受监测。没有根据肿瘤大小标准进行切除的患者发生转移。PNET患者更有可能发生错义突变（58%），5例有转移性疾病的患者中有4例（80%）在外显子3中有突变，而39例无转移性疾病的患者中有18例（46%）在外显子3中有突变。
基于大小标准的检测成像和手术切除已成功管理了VHL合并PNET的患者。种系突变分析可能有助于识别有PNET风险的患者以及哪些患者可能从手术干预中获益。
