Clinical Genetics, LUMC, Leiden, The Netherlands
Clinical Genetics, LUMC, Leiden, The Netherlands.
J Clin Pathol. 2021 Nov;74(11):724-729. doi: 10.1136/jclinpath-2020-207040. Epub 2020 Oct 12.
Previous estimates of the prevalence of mismatch repair (MMR) deficiency and Lynch syndrome in small bowel cancer have varied widely. The aim of this study was to establish the prevalence of MMR deficiency and Lynch syndrome in a large group of small bowel adenocarcinomas.
To this end, a total of 400 small bowel adenocarcinomas (332 resections, 68 biopsies) were collected through the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief (PALGA)). No preselection criteria, such as family history, were applied, thus avoiding (ascertainment) bias. MMR deficiency status was determined by immunohistochemical staining of MMR proteins, supplemented by promoter hypermethylation analysis and next generation sequencing of the MMR genes.
MMR deficiency was observed in 22.3% of resected and 4.4% of biopsied small bowel carcinomas. Prevalence of Lynch syndrome was 6.2% in resections and 0.0% in biopsy samples. Patients with Lynch syndrome-associated small bowel cancer were significantly younger at the time of diagnosis than patients with MMR-proficient and sporadic MMR-deficient cancers (mean age of 54.6 years vs 66.6 years and 68.8 years, respectively, p<0.000).
The prevalence of MMR deficiency and Lynch syndrome in resected small bowel adenocarcinomas is at least comparable to prevalence in colorectal cancers, a finding relevant both for treatment (immunotherapy) and family management. We recommend that all small bowel adenocarcinomas should be screened for MMR deficiency.
先前对小肠腺癌中错配修复（MMR）缺陷和林奇综合征的患病率的估计差异很大。本研究旨在确定大量小肠腺癌中 MMR 缺陷和林奇综合征的患病率。
为此，通过荷兰全国组织病理学和细胞学登记处（Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief（PALGA））共收集了 400 例小肠腺癌（332 例切除，68 例活检）。未应用家族史等预选标准，从而避免了（确定）偏倚。通过 MMR 蛋白的免疫组织化学染色，辅以启动子超甲基化分析和 MMR 基因的下一代测序来确定 MMR 缺陷状态。
在切除的和活检的小肠腺癌中分别观察到 MMR 缺陷 22.3%和 4.4%。在切除标本中林奇综合征的患病率为 6.2%，在活检样本中为 0.0%。与 MMR 功能正常和散发性 MMR 缺陷的癌症患者相比，林奇综合征相关的小肠癌患者的诊断年龄明显较小（平均年龄分别为 54.6 岁、66.6 岁和 68.8 岁，p<0.000）。
在切除的小肠腺癌中 MMR 缺陷和林奇综合征的患病率至少与结直肠癌的患病率相当，这一发现与治疗（免疫疗法）和家族管理均相关。我们建议所有小肠腺癌都应进行 MMR 缺陷筛查。
