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

• Published in: Hereditary cancer in clinical practice 2023-10, Vol.21 (1), p.1-20, Article 20
• Main Authors: Oka, Suguru, Urakami, Shinji, Hagiwara, Kiichi, Hayashida, Michikata, Sakaguchi, Kazushige, Miura, Yuji, Inoshita, Naoko, Arai, Masami
• Format: Article
• Language: English
• Subjects: Autosomal dominant inheritance; Cancer; Cancer patients; Colon cancer; Colorectal cancer; Diagnosis; DNA; DNA mismatch repair; DNA repair; Gene mutations; Genes; Genetic aspects; Genetic disorders; Genetic screening; Genetic testing; Immunohistochemistry; Lynch syndrome; Mismatch repair; MLH1 protein; MMR protein; MSH2 protein; MSH6 protein; Mutation; Oncology, Experimental; Pathology; Prostate cancer; Prostatectomy; Protein deficiency; Proteins; Yeast
• ISSN: 1897-4287; 1731-2302; 1897-4287
• DOI: 10.1186/s13053-023-00265-1

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. Keywords: Prostate cancer, Lynch syndrome, DNA mismatch repair