Universal testing in endometrial cancer in Sweden.

IF 2 4区医学 Q3 ONCOLOGY

Hereditary Cancer in Clinical Practice Pub Date : 2024-08-22 DOI:10.1186/s13053-024-00288-2

Emil Andersson, Anne Keränen, Kristina Lagerstedt-Robinson, Sam Ghazi, Annika Lindblom, Emma Tham, Miriam Mints

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Abstract

Background: The aim of the study was to test a universal screening strategy on endometrial cancer to evaluate its effectiveness to find Lynch Syndrome (LS) cases to two established clinical criteria: Amsterdam II criteria, and the revised Bethesda criteria to select cases for prescreening with immunohistochemistry (IHC). Cases were subsequently screened for germline disease causing variants regarding the DNA mismatch repair (MMR) genes.

Methods: IHC was performed on 221 endometrial cancer (EC) cases, using antibodies against the DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. MMR loss was found in 54 cases, and gene mutation screening was undertaken in 52 of those.

Results: In this set of patients, the use of Amsterdam II criteria detected two (0.9%), the Bethesda criteria two (0.9%), and universal testing five (2.3%) cases of LS. The combination of universal testing and family history criteria resulted in detection of five patients (2.3%) with LS.

Conclusions: Based on our results and other similar studies to date we propose a screening protocol for LS on EC tumors with prescreening using IHC for the four MMR proteins on all new EC cases diagnosed before 70 years of age, followed by mutation screening of all tumors with loss of MSH2 and/or MSH6 or only PMS2, plus consideration for mutation screening of all LS genes in cases fulfilling the clinical Amsterdam II criteria regardless of MMR status on IHC.

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瑞典子宫内膜癌的普遍检测。

研究背景该研究的目的是测试子宫内膜癌的普遍筛查策略，以评估其根据两个既定临床标准发现林奇综合征（LS）病例的有效性：阿姆斯特丹 II 标准和修订后的贝塞斯达标准，选择病例进行免疫组化（IHC）预检。随后对病例进行 DNA 错配修复（MMR）基因种系致病变异筛查：使用针对 DNA 错配修复蛋白 MLH1、PMS2、MSH2 和 MSH6 的抗体对 221 例子宫内膜癌（EC）病例进行了 IHC 检测。54例患者发现了MMR缺失，其中52例进行了基因突变筛查：结果：在这组患者中，使用阿姆斯特丹II标准发现了2例（0.9%）LS，贝塞斯达标准发现了2例（0.9%），普遍检测发现了5例（2.3%）。将普遍检测和家族史标准结合使用，结果发现了5例（2.3%）LS患者：根据我们的研究结果和迄今为止的其他类似研究，我们提出了EC肿瘤LS的筛查方案，即对所有70岁以前确诊的EC新病例使用IHC对四种MMR蛋白进行预筛查，然后对所有缺失MSH2和/或MSH6或仅缺失PMS2的肿瘤进行突变筛查，并考虑对符合阿姆斯特丹II临床标准的病例进行所有LS基因的突变筛查，无论IHC上的MMR状态如何。

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

Hereditary Cancer in Clinical Practice 医学-肿瘤学

CiteScore

3.10

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.