Chika Noriyasu, Eguchi Hidetaka, Kumamoto Kensuke, Suzuki Okihide, Ishibashi Keiichiro, Tachikawa Tetsuhiko, Akagi Kiwamu, Tamaru Jun-Ichi, Okazaki Yasushi, Ishida Hideyuki
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Japan.
Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Japan.
Jpn J Clin Oncol. 2017 Feb 9;47(2):108-117. doi: 10.1093/jjco/hyw178.
We investigated the prevalence of Lynch syndrome and Lynch-like syndrome among Japanese colorectal cancer patients, as there have been no credible data from Japan.
Immunohistochemical analyses for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) were carried out in surgically resected, formalin-fixed paraffin-embedded specimens obtained from 1,234 newly diagnosed colorectal cancer patients between March 2005 and April 2014. The presence/absence of the BRAF V600E mutation and hypermethylation of the MLH1 promoter was analyzed where necessary. Genetic testing was finally undertaken in patients suspected as having Lynch syndrome.
By the universal screening approach with immunohistochemical analysis for mismatch repair proteins followed by analyses for the BRAF V600E mutation and MLH1 promoter methylation status, 11 (0.9%) of the 1,234 patients were identified as candidates for genetic testing. Out of the 11 patients, 9 (0.7%) were finally diagnosed as having Lynch syndrome; the responsible genes included MLH1 (n = 1), MSH2 (n = 4), EPCAM (n = 1) and MSH6 (n = 3). The remaining two patients (0.2%) were regarded as having Lynch-like syndrome, since biallelic somatic deletion of the relevant mismatch repair genes was detected in the absence of germline mismatch repair alterations. None of the cases was identified as having germline MLH1 epimutation.
The prevalence of Lynch syndrome among all newly diagnosed cases of colorectal cancer in Japan is in the same range as that recently reported by studies in Western population. The prevalence of Lynch-like syndrome seems to be extremely low.
由于日本尚无可靠数据，我们调查了日本结直肠癌患者中林奇综合征和林奇样综合征的患病率。
对2005年3月至2014年4月期间1234例新诊断的结直肠癌患者手术切除的、经福尔马林固定石蜡包埋的标本进行错配修复蛋白（MLH1、MSH2、MSH6和PMS2）的免疫组织化学分析。必要时分析BRAF V600E突变的存在与否以及MLH1启动子的甲基化情况。最终对疑似患有林奇综合征的患者进行基因检测。
通过对错配修复蛋白进行免疫组织化学分析，随后分析BRAF V600E突变和MLH1启动子甲基化状态的通用筛查方法，在1234例患者中有11例（0.9%）被确定为基因检测候选者。在这11例患者中，9例（0.7%）最终被诊断为患有林奇综合征；致病基因包括MLH1（n = 1）、MSH2（n = 4）、EPCAM（n = 1）和MSH6（n = 3）。其余2例患者（0.2%）被视为患有林奇样综合征，因为在不存在种系错配修复改变的情况下检测到相关错配修复基因的双等位基因体细胞缺失。所有病例均未被确定为患有种系MLH1表型突变。
日本所有新诊断的结直肠癌病例中林奇综合征的患病率与最近西方人群研究报告的患病率范围相同。林奇样综合征的患病率似乎极低。
