Durhuus Jon Ambæk, Galanakis Michael, Maltesen Thomas, Therkildsen Christina, Rosthøj Susanne, Klarskov Louise Laurberg, Lautrup Charlotte Kvist, Andersen Ove, Nilbert Mef Christina
Department of Clinical Research, Copenhagen University Hospital - Amager and Hvidovre, Kettegårds Allé 30, Copenhagen 2630, Denmark; Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
Danish Cancer Institute, Statistics and Data Analysis, Copenhagen, Denmark.
Transl Oncol. 2024 Aug;46:102013. doi: 10.1016/j.tranon.2024.102013. Epub 2024 Jun 1.
Universal screening for defective mismatch repair (dMMR) in colorectal cancer utilizes immunohistochemical staining for MLH1, MSH2, MSH6 and PSM2. Additionally, BRAF V600E mutations status and MLH1 hypermethylation should be performed to distinguish germline and somatic dMMR alterations. A decade of Danish population-based registries has been analysed regarding screening uptake, detection rate and referral to genetic counselling. MMR testing was performed in 71·8% (N = 34,664) of newly diagnosed colorectal cancers with an increasing trend to 88·8% coverage in the study's final year. The likelihood of undergoing MMR testing was reduced in males with 2% (95% CI 0·4-2·7, p = 0·008), with 4·1% in patients above age 70 years (95% CI 1·5-6·6, p = 0·003) compared in patients below age 51 years, with 16·3% in rectal cancers (95% CI 15·1-17·6, p < 0·001) and 1·4% left-sided colon cancers (95% CI 0·1-1·7, p = 0·03) compared to right-sided colon cancers. Tumour stage II and III increased the likelihood of being tested, with 3·7% for stage II (95% CI 2·2-5·6, p < 0·001) and 3·3% for stage III tumours (95% CI 1·8-4·8, p < 0·001) compared to stage I tumours, whereas the likelihood for stage IV tumours is reduced by 35·7% (95% CI 34·2-37·2, p < 0·001). Test rates significantly differed between the Danish health care regions. dMMR was identified in 15·1% (95% CI 14·8-15·6, p < 0·001) cases with somatic MMR inactivation in 6·7% of the cases. 8·3% tumours showed hereditary dMMR expression patterns, and 20·0% of those were referred to genetic counselling. Despite the high uptake rates, we found disparities between patient groups and missed opportunities for genetic diagnostics.
结直肠癌中缺陷性错配修复（dMMR）的普遍筛查采用对MLH1、MSH2、MSH6和PSM2进行免疫组织化学染色。此外，应检测BRAF V600E突变状态和MLH1高甲基化，以区分种系和体细胞dMMR改变。对丹麦基于人群的十年登记数据进行了分析，内容涉及筛查接受率、检出率以及转介至遗传咨询的情况。在71.8%（N = 34,664）的新诊断结直肠癌中进行了错配修复（MMR）检测，在研究的最后一年覆盖率呈上升趋势，达到88.8%。男性接受MMR检测的可能性降低了2%（95%置信区间0.4 - 2.7，p = 0.008），70岁以上患者为4.1%（95%置信区间1.5 - 6.6，p = 0.003），而51岁以下患者为16.3%；直肠癌患者为16.3%（95%置信区间15.1 - 17.6，p < 0.001），左侧结肠癌患者为1.4%（95%置信区间0.1 - 1.7，p = 0.03），与右侧结肠癌相比。肿瘤II期和III期增加了检测的可能性，II期为3.7%（95%置信区间2.2 - 5.6，p < 0.001），III期肿瘤为3.3%（95%置信区间1.8 - 4.8，p < 0.001），与I期肿瘤相比，而IV期肿瘤的可能性降低了35.7%（95%置信区间34.2 - 37.2，p < 0.001）。丹麦各医疗保健地区的检测率存在显著差异。在15.1%（95%置信区间为14.8 - 15.6，p < 0.001）的病例中鉴定出dMMR，6.7%的病例存在体细胞MMR失活。8.3%的肿瘤显示出遗传性dMMR表达模式，其中20.0%被转介至遗传咨询。尽管接受率较高，但我们发现不同患者群体之间存在差异，并且存在遗传诊断的错失机会。
