Pancreatobiliary Cancer Clinic, Department of Surgery, Gangnam Severance Hospital, Yonsei University Health System, Seoul, Korea.
Ann Surg Oncol. 2013 Aug;20(8):2511-7. doi: 10.1245/s10434-013-2908-7. Epub 2013 Mar 12.
Bile duct cancer has very poor prognosis. Important prognostic factors include the TNM stage, cell differentiation, and histologic type; however, we often observe patients whose prognosis is not consistent with the TNM stage. Additional prognostic indicators are mandatory to complement those used presently. We evaluated the hypermethylation status of genes for the power to predict overall survival following curative resection of mid/distal bile duct cancer.
Pyrosequencing hypermethylation status at the loci of interest was analyzed in 65 mid/distal bile duct carcinoma specimens obtained at Severance Hospital of Yonsei University College of Medicine from January 2000 to December 2006.
Significant methylation frequencies (MtI >5 %) were obtained for 5 genes (which P16 [17 %], DAPK [54 %], E-cadherin [60 %], RASSF-1 [46.2 %], and hMLH1 [43.1 %]). MtI status of P16, DAPK, and RASSF-1 were correlated with perineural invasion, tumor depth, and age, respectively. In the multivariate analysis of overall survival, the presence of lymph node metastasis and P16 methylation status were identified as independent prognostic factors for overall survival. Patients with unmethylated of P16 had the 3- and 5-year survival rates of 60.8 and 54.9 %, respectively. In patients with hypermethylated P16, the 3- and 5-year survival rates were 27.3 and 0.0 %, respectively.
P16 hypermethylation and lymph node metastasis may predict overall survival in curative resected mid/distal bile duct cancer. Classification of mid/distal bile duct cancer by both genetic and epigenetic profiles may improve the accuracy in predicting outcome and the effectiveness of tailored therapy in these diseases.
胆管癌预后极差。重要的预后因素包括 TNM 分期、细胞分化和组织学类型；然而，我们经常观察到一些患者的预后与 TNM 分期不一致。需要额外的预后指标来补充目前使用的指标。我们评估了中远端胆管癌根治性切除术后整体生存的基因高甲基化状态，以预测其预后。
分析了 2000 年 1 月至 2006 年 12 月在延世大学医学院 Severance 医院获得的 65 例中远端胆管癌标本中感兴趣的基因的焦磷酸测序高甲基化状态。
5 个基因（P16[17%]、DAPK[54%]、E-cadherin[60%]、RASSF-1[46.2%]和 hMLH1[43.1%]）的甲基化频率（MtI>5%）显著。P16、DAPK 和 RASSF-1 的 MtI 状态分别与神经周围侵犯、肿瘤深度和年龄有关。在总生存的多变量分析中，淋巴结转移和 P16 甲基化状态被确定为总生存的独立预后因素。P16 未甲基化的患者 3 年和 5 年的生存率分别为 60.8%和 54.9%。P16 高甲基化的患者 3 年和 5 年的生存率分别为 27.3%和 0.0%。
P16 甲基化和淋巴结转移可能预测中远端胆管癌根治性切除术后的总生存。对中远端胆管癌进行遗传和表观遗传特征分类可能会提高预测结果的准确性，并提高针对这些疾病的靶向治疗的效果。
