Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Surg Res. 2011 Apr;166(2):e121-7. doi: 10.1016/j.jss.2010.11.898. Epub 2010 Dec 18.
Current available preoperative diagnostic workup is insufficient to differentiate between benign and malignant pancreatic neuroendocrine tumors (PNET). The aim of the present study was to evaluate the potential prognostic role of the promoter GTn repeat polymorphism (GTn) of the heme oxygenase-1 gene in PNET.
Tumor, metastasis, corresponding healthy tissue, and peripheral blood leukocyte DNA of 46 patients who underwent surgical resection for PNET were analyzed for GTn by PCR, capillary electrophoresis, and DNA-sequencing. The GTn was correlated to clinicopathologic parameters and clinical outcome.
GTn was classified into short (<25) and long (≥ 25) alleles and three (SS, SL, and LL) genotypes were defined. There was no difference in GTn genotype among tumor, healthy tissue, metastasis, and peripheral blood leukocyte DNA. The SS and SL genotype displayed significantly more poor differentiated tumors (P = 0.001) and higher tumor recurrence rate (P = 0.0001) compared with LL patients. The LL genotype patients presented predominantly benign PNET (P < 0.001). The LL genotype had the longest disease-free (P < 0.001) and overall survival (P = 0.006). Besides the WHO classification the GTn was identified as a strong predictor of tumor recurrence (hazard ratio 3.1, 95% confidence interval 1.3-7.3) in PNET.
GTn differentiates between benign and malignant PNET and is a strong predictor of tumor recurrence.
目前可用的术前诊断方法不足以区分胰腺神经内分泌肿瘤（PNET）的良恶性。本研究旨在评估血红素加氧酶-1 基因启动子 GTn 重复多态性（GTn）在 PNET 中的潜在预后作用。
对 46 例接受 PNET 手术切除的患者的肿瘤、转移灶、相应的健康组织和外周血白细胞 DNA 进行 PCR、毛细管电泳和 DNA 测序分析 GTn。将 GTn 与临床病理参数和临床结果相关联。
GTn 分为短（<25）和长（≥25）等位基因，定义了三种（SS、SL 和 LL）基因型。肿瘤、健康组织、转移灶和外周血白细胞 DNA 中 GTn 基因型无差异。与 LL 患者相比，SS 和 SL 基因型的肿瘤分化程度较差（P=0.001），肿瘤复发率较高（P=0.0001）。LL 基因型患者主要表现为良性 PNET（P<0.001）。LL 基因型患者的无病生存期（P<0.001）和总生存期（P=0.006）最长。除了 WHO 分级外，GTn 也被确定为 PNET 肿瘤复发的强预测因子（危险比 3.1，95%置信区间 1.3-7.3）。
GTn 可区分良恶性 PNET，是肿瘤复发的强预测因子。
