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Abstract：
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.
摘要：
结肠直肠癌中缺陷错配修复(dMMR)的通用筛查利用MLH1、MSH2、MSH6和PSM2的免疫组织化学染色。此外,应进行BRAFV600E突变状态和MLH1超甲基化以区分种系和体细胞dMMR改变。十年来的丹麦人口登记册已经被分析了关于筛查的吸收，检出率和转诊遗传咨询。在新诊断的结直肠癌中进行了71·8％（N=34,664）的MMR测试，在研究的最后一年中覆盖率呈上升趋势，达到88·8％。男性接受MMR测试的可能性降低了2％（95％CI0·4-2·7，p=0·008），与年龄在51岁以下的患者相比，70岁以上的患者为4·1％（95％CI1·5-6·6，p=0·003），与右侧结肠癌相比，直肠癌为16·3%(95%CI15·1-17·6，p<0·001)，左侧结肠癌为1·4%(95%CI0·1-1·7，p=0·03)。II期和III期肿瘤增加了被检测的可能性，与I期肿瘤相比，II期3·7%(95%CI2·2-5·6，p<0·001)和III期肿瘤3·3%(95%CI1·8-4·8，p<0·001)，而IV期肿瘤的可能性降低了35·7%（95%CI34·2-37·2，p<0·001）。丹麦医疗保健地区之间的测试率差异很大。在15·1%(95%CI14·8-15·6，p<0·001)的病例中发现了dMMR，在6·7%的病例中发现了体细胞MMR失活。8·3%肿瘤显示遗传性dMMR表达模式，20·0%的患者接受了遗传咨询。尽管吸收率很高，我们发现患者组之间存在差异,并且错过了基因诊断的机会.
