The prevalence of lynch syndrome (DNA mismatch repair protein deficiency) in patients with primary localized prostate cancer using immunohistochemistry screening.

IF 2 4区医学 Q3 ONCOLOGY

Hereditary Cancer in Clinical Practice Pub Date : 2023-10-12 DOI:10.1186/s13053-023-00265-1

Suguru Oka, Shinji Urakami, Kiichi Hagiwara, Michikata Hayashida, Kazushige Sakaguchi, Yuji Miura, Naoko Inoshita, Masami Arai

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Abstract

Background: Prostate cancer is one of the most heritable human cancers. Lynch syndrome is an autosomal dominant inheritance caused by germline mutations in DNA mismatch repair (MMR) genes, which are also associated with an increased incidence of prostate cancer. However, prostate cancer has not been defined as a Lynch syndrome-associated cancer. The proportion of Lynch syndrome patients in primary prostate cancers is unclear. In this study, we investigated MMR protein loss using universal immunohistochemical screening to determine the prevalence of Lynch syndrome in patients with localized prostate cancer who underwent radical prostatectomy.

Methods: One hundred twenty-nine surgical specimens from radical prostatectomy performed at Toranomon Hospital between 2012 and 2015 were retrospectively tested using universal screening with immunohistochemistry staining for expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6. For all suspected MMR-deficient patients, germline genetic tests focusing on MMR genes were performed.

Results: MMR protein loss was found in only one patient (0.8%) who showed dual MSH2/MSH6 loss. This patient showed a single nucleotide pathogenic germline mutation from c.1129 C to T (p.Gln377*) at exon 7 in the MSH2 gene. He was diagnosed with a primary prostate cancer at 66 years of age. He had a documented history of Lynch syndrome (Muir-Torre syndrome) with previous colon cancer, sebaceous tumor, and keratoacanthoma as well as subsequent bladder cancer, all of which also showed dual MSH2/MSH6 loss. He also had a strong family history of colorectal and other Lynch syndrome-associated cancers. The pathological stage was pT3aN0M0, and the pathological grade was Gleason 7(4 + 3) with tertiary pattern 5.

Conclusions: In this study, immunohistochemical screening of MMR proteins for Lynch syndrome was performed in a series of prostate cancer cases. The prevalence of Lynch syndrome in localized prostate cancer was 0.8%, which is low compared with other Lynch syndrome-associated cancers.

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应用免疫组化筛查原发性局限性前列腺癌症患者的林奇综合征（DNA错配修复蛋白缺乏）的患病率。

背景：癌症是人类最易遗传的癌症之一。林奇综合征是一种由DNA错配修复（MMR）基因种系突变引起的常染色体显性遗传，也与癌症发病率增加有关。然而，前列腺癌症尚未被定义为林奇综合征相关的癌症。林奇综合征患者在原发性前列腺癌中的比例尚不清楚。在这项研究中，我们使用通用免疫组织化学筛查来研究MMR蛋白损失，以确定接受根治性前列腺切除术的局限性前列腺癌症患者林奇综合征的患病率。方法：使用免疫组织化学染色的通用筛查方法，对2012年至2015年间在Toranomon医院进行的129例根治性前列腺切除术的手术标本进行MMR蛋白MLH1、PMS2、MSH2和MSH6表达的回顾性检测。对于所有疑似MMR缺乏的患者，进行了以MMR基因为重点的种系遗传测试。结果：只有一名患者（0.8%）出现MSH2/MSH6双重缺失，MMR蛋白缺失。该患者在MSH2基因的外显子7处表现出从c.1129C到T（p.Gln377*）的单核苷酸致病性种系突变。他在66岁时被诊断为原发性前列腺癌癌症。他有林奇综合征（Muir-Torre综合征）病史，既往结肠癌癌症、皮脂腺肿瘤、角质棘皮瘤以及随后的癌症，所有这些都显示MSH2/MSH6双重缺失。他还有结直肠癌和其他林奇综合征相关癌症的家族史。病理分期为pT3aN0M0，病理分级为Gleason 7级（4 + 3）结论：本研究对一系列前列腺癌症患者进行了林奇综合征MMR蛋白的免疫组化筛查。林奇综合征在局限性前列腺癌症中的患病率为0.8%，与其他林奇综合症相关癌症相比，这是较低的。

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.