Tan Xiaoli, Fang Yongzhen, Fan Xinjuan, Deng Weihao, Huang Jinglin, Cai Yacheng, Zou Jiaxin, Chen Zhiting, Lin Hanjie, Xu Liang, Wang Guannan, Zhan Huanmiao, Huang Shuhui, Fu Xinhui
Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
Gastroenterol Rep (Oxf). 2024 Apr 2;12:goae011. doi: 10.1093/gastro/goae011. eCollection 2024.
promoter methylation analysis is recommended in screening for Lynch syndrome (LS) in patients with MLH1-deficient colorectal cancer (CRC). The study aims to identify specific methylation regions in the promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with methylation.
A total of 580 CRC cases were included. The DNA mismatch repair (MMR) protein expression was assessed by using immunohistochemistry (IHC). The methylation status of the Regions A, B, C, D, and E in the promoter was tested by using bisulfite sequencing PCR. The specificities of the five regions were calculated. Associations between methylation and clinicopathologic characteristics were evaluated. Kaplan-Meier analyses for overall survival (OS) were carried out.
In 580 CRC cases, the specificities of the methylation test in Regions D and E were both 97.8%. In the MLH1-deficient CRCs, the frequencies of methylation and mutation were 52.6% and 14.6%, respectively; mutation occurred in 27.7% of patients with -methylated CRC. In the MMR-deficient patients, compared with unmethylation, methylation was more common in patients who were aged ≥50 years, female, had no family history of LS-related tumors, and had tumors located at the right colon. In the MMR-deficient patients, the -methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors (=0.047).
Regions D and E in the promoter are recommended for determining the methylation status in screening for LS in MLH1-deficient CRC. In MMR-deficient patients, the -methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.
对于错配修复蛋白1（MLH1）缺陷型结直肠癌（CRC）患者，推荐进行启动子甲基化分析以筛查林奇综合征（LS）。本研究旨在确定启动子中的特定甲基化区域，并评估甲基化患者的临床病理特征及预后。
共纳入580例CRC病例。采用免疫组织化学（IHC）评估DNA错配修复（MMR）蛋白表达。通过亚硫酸氢盐测序PCR检测启动子中A、B、C、D和E区域的甲基化状态。计算这五个区域的特异性。评估甲基化与临床病理特征之间的关联。进行总生存（OS）的Kaplan-Meier分析。
在580例CRC病例中，D区域和E区域甲基化检测的特异性均为97.8%。在MLH1缺陷型CRC中，甲基化和突变的频率分别为52.6%和14.6%；27.7%的甲基化CRC患者发生了突变。在MMR缺陷患者中，与未甲基化相比，甲基化在年龄≥50岁、女性、无LS相关肿瘤家族史且肿瘤位于右半结肠的患者中更为常见。在MMR缺陷患者中，有LS相关肿瘤家族史的甲基化病例的OS率低于未甲基化病例（P = 0.047）。
推荐使用启动子中的D区域和E区域来确定MLH1缺陷型CRC筛查中LS的甲基化状态。在MMR缺陷患者中，有LS相关癌症家族史的甲基化病例的OS比未甲基化病例更差。
