Streamlining the diagnostic pathway for Lynch syndrome in colorectal cancer patients: a 10-year experience in a single Italian Cancer Center.

IF 2.1 4区医学 Q3 ONCOLOGY

European Journal of Cancer Prevention Pub Date : 2024-07-01 Epub Date: 2024-01-09 DOI:10.1097/CEJ.0000000000000870

Alberto Puccini, Simone Nardin, Lucia Trevisan, Sonia Lastraioli, Viviana Gismondi, Ilaria Ricciotti, Azzurra Damiani, Giacomo Bregni, Roberto Murialdo, Alessandro Pastorino, Valentino Martelli, Annalice Gandini, Luca Mastracci, Liliana Varesco, Maria Dono, Linda Battistuzzi, Federica Grillo, Stefania Sciallero

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引用次数: 0

Abstract

Background: Universal screening of colorectal cancer (CRC) patients for Lynch syndrome (LS) through MisMatch Repair (MMR) testing is recommended. BRAF V600E mutation and/or MLH1 promoter methylation (Reflex Testing, RefT)generally rule out LS in MLH1-deficient (dMLH1) patients. We estimated the impact of RefTon genetic counseling (GC) and on the diagnostic yield of genetic testing (GT).

Methods: Overall, 3199 CRC patients were referred to our center between 2011 and 2021. Patients referred until January 2019 (n=2536) underwent universal MMR testing and were termed 'Cohort A'; among patients after February 2019 (n=663), 'Cohort B', RefT was also performed in dMLH1 patients.

Results: Overall, 401/3199 patients (12.5%) were MMR-deficient (dMMR); 312 (77.8%) in cohort A and 89 (22.2%) inB; 346/401 were dMLH1 (86.3%), 262/312 (83.9%) in cohort A and 84/89 (94.3%) in B. In Cohort A, 91/312 (29.1%) dMMR patients were referred to GC, 69/91 (75.8%) were in the dMLH1 group; 57/69 (82.6%) dMLH1 patients underwent GT and 1/57 (1.7%) had LS. In Cohort B, 3/84 dMLH1 patients did not undergo BRAF testing. Three BRAF wt and not hypermethylated of the remaining 81 dMLH1 patients were referred to GC and GT, and one had LS. This diagnostic pathway reduced GC referrals by 96% (78/81) in Cohort B and increased the diagnostic yield of GT by about 20 times.

Conclusion: Our findings support RefT in dMLH1 CRC patients within the LS diagnostic pathway, as it reduces the number of GC sessions needed and increases the diagnostic yield of GT.

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简化结直肠癌患者林奇综合征的诊断路径：意大利一家癌症中心的十年经验。

背景：建议通过错配修补（MMR）检测对结直肠癌（CRC）患者进行林奇综合征（LS）普查。BRAFV600E突变和/或MLH1启动子甲基化（反射检测，RefT）通常可排除MLH1缺陷（dMLH1）患者的LS。我们估算了 RefT 对遗传咨询（GC）和遗传检测（GT）诊断率的影响：2011年至2021年间，共有3199名CRC患者转诊至本中心。2019年1月之前转诊的患者（n=2536）接受了MMR通用检测，被称为 "队列A"；2019年2月之后的患者（n=663）被称为 "队列B"，对dMLH1患者也进行了RefT：总体而言，401/3199 例患者（12.5%）为 MMR 缺乏（dMMR），A 组群中有 312 例（77.8%），B 组群中有 89 例（22.2%）；346/401 例患者为 dMLH1（86.3%），A 组群中有 262/312 例（83.9%），B 组群中有 84/89 例（94.3%）。在队列 A 中，91/312（29.1%）名 dMMR 患者被转至 GC，69/91（75.8%）名 dMLH1 组；57/69（82.6%）名 dMLH1 患者接受了 GT，1/57（1.7%）名患者接受了 LS。在队列 B 中，3/84 的 dMLH1 患者没有接受 BRAF 检测。剩余的 81 名 dMLH1 患者中，有 3 名 BRAF 含量为 wt 且未发生高甲基化的患者被转诊至 GC 和 GT，1 名患者进行了 LS。在队列 B 中，这种诊断途径将 GC 转诊率降低了 96%（78/81），并将 GT 的诊断率提高了约 20 倍：我们的研究结果支持在 LS 诊断路径下对 dMLH1 CRC 患者进行 RefT，因为它减少了所需的 GC 治疗次数，提高了 GT 的诊断率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Cancer Prevention 医学-肿瘤学

CiteScore

4.10

自引率

4.20%

发文量

审稿时长

1 months

期刊介绍： European Journal of Cancer Prevention aims to promote an increased awareness of all aspects of cancer prevention and to stimulate new ideas and innovations. The Journal has a wide-ranging scope, covering such aspects as descriptive and metabolic epidemiology, histopathology, genetics, biochemistry, molecular biology, microbiology, clinical medicine, intervention trials and public education, basic laboratory studies and special group studies. Although affiliated to a European organization, the journal addresses issues of international importance.