Oka Suguru, Urakami Shinji, Hagiwara Kiichi, Hayashida Michikata, Sakaguchi Kazushige, Miura Yuji, Inoshita Naoko, Arai Masami
Department of Urology, Toranomon Hospital, 2-2-2 Toranomon Minato-ku, 105-8470, Tokyo, Japan.
Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon Minato-ku, 105-8470, Tokyo, Japan.
Hered Cancer Clin Pract. 2023 Oct 12;21(1):20. doi: 10.1186/s13053-023-00265-1.
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.
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.
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.
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.
前列腺癌是最具遗传性的人类癌症之一。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疾病，其也与前列腺癌发病率增加相关。然而，前列腺癌尚未被定义为林奇综合征相关癌症。原发性前列腺癌中林奇综合征患者的比例尚不清楚。在本研究中，我们通过通用免疫组化筛查调查MMR蛋白缺失情况，以确定接受根治性前列腺切除术的局限性前列腺癌患者中林奇综合征的患病率。
回顾性检测2012年至2015年在虎之门医院进行的129例根治性前列腺切除术的手术标本，采用通用免疫组化筛查检测MMR蛋白MLH1、PMS2、MSH2和MSH6的表达。对于所有疑似MMR缺陷患者，进行聚焦于MMR基因的种系基因检测。
仅在1例患者（0.8%）中发现MMR蛋白缺失，该患者表现为MSH2/MSH6双重缺失。该患者在MSH2基因第7外显子处有一个从c.1129 C到T（p.Gln377*）的单核苷酸致病性种系突变。他66岁时被诊断为原发性前列腺癌。他有林奇综合征（穆尔-托雷综合征）病史，既往有结肠癌、皮脂腺瘤和角化棘皮瘤，随后又患膀胱癌，所有这些肿瘤也都表现为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（4+3），三级模式为5级。
在本研究中，我们对一系列前列腺癌病例进行了MMR蛋白免疫组化筛查以检测林奇综合征。局限性前列腺癌中林奇综合征的患病率为0.8%，与其他林奇综合征相关癌症相比相对较低。
