CDH1 truncating mutations in the E-cadherin gene - An indication for total gastrectomy to treat hereditary diffuse gastric cancer
CDH1 truncating mutations in the E-cadherin gene - An indication for total gastrectomy to treat hereditary diffuse gastric cancer
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DOI：
10.1097/01.sla.0000254370.29893.e4
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发表时间：
2007-06-01
影响因子：
9
通讯作者：
Ford, James M.
中科院分区：
文献类型：
--
作者：
Norton, Jeffrey A.;Ham, Christine M.;Ford, James M.
背景：大约1%-3%的胃癌与常染色体显性遗传易感性家族有关。E-cadherin（CDH 1）截短突变已被证明存在于约30%的遗传性弥漫性胃癌（HDGC）家族中，并与胃癌和小叶乳腺癌的风险显著增加相关。来自HDGC大家族的被鉴定为具有CDH 1突变的个体前瞻性地进行了粪便潜血试验的全面筛查，标准上消化道内窥镜检查和随机胃活检、高倍镜检查和随机胃活检、超声内镜检查、CT和PET扫描，以评估胃的隐匿性癌症。随后，他们都接受了全胃切除术与D-2淋巴结清扫和Roux-en-y食管空肠吻合术。结果：6例患者均为同一家系的CDH 1携带者。有2名男性和4名女性。平均年龄为54岁（范围：51-57岁）。没有患者有任何胃癌的体征或症状。每例患者的详尽术前胃评估均正常，手术时胃和邻近淋巴结显示正常。然而，每例患者（6/6，100%）被发现有多个病灶的T1浸润性弥漫性胃腺癌（纯印戒细胞型）。无淋巴结或远处转移。每一个都被分期为T1 N 0 M0。每个病人恢复顺利，没有发病率或mortals.Conclusions：CDH 1基因突变的个体HDGC的家庭与胃癌在一个高度渗透的方式。CDH 1突变是这些患者进行全胃切除术的指征。这种突变将在其他可检测到的癌症症状或体征之前识别出癌症患者。
Background: Approximately 1% to 3% of all gastric cancers are associated with families exhibiting an autosomal dominant pattern of susceptibility. E-cadherin (CDH1) truncating mutations have been shown to be present in approximately 30% of families with hereditary diffuse gastric cancer (HDGC) and are associated with a significantly increased risk of gastric cancer and lobular breast cancer.Methods: Individuals from a large kindred with HDGC who were identified to have a CDH1 mutation prospectively underwent comprehensive screening with stool occult blood testing, standard upper gastrointestinal endoscopy with random gastric biopsies, high-magnification endoscopy with random gastric biopsies, endoscopic ultrasonography, CT, and PET scans to evaluate the stomach for occult cancer. Subsequently, they each underwent total gastrectomy with D-2 node dissection and Roux-en-y esophagojejunostomy. The stomach and resected lymph nodes were evaluated pathologically.Results: Six patients were identified as CDH1 carriers from a single family. There were 2 men and 4 women. The mean age was 54 years (range, 51-57 years). No patient had any signs or symptoms of gastric cancer. Exhaustive preoperative stomach evaluation was normal in each case, and the stomach and adjacent lymph nodes appeared normal at surgery. However, each patient (6 of 6, 100%) was found to have multiple foci of T1 invasive diffuse gastric adenocarcinoma (pure signet-ring cell type). No patient had lymph node or distant metastases. Each was staged as T1N0M0. Each patient recovered uneventfully without morbidity or mortality.Conclusions: CDH1 mutations in individuals from families with HDGC are associated with gastric cancer in a highly penetrant fashion. CDH1 mutations are an indication for total gastrectomy in these patients. This mutation will identify patients with cancer before other detectable symptoms or signs of the disease.