Frequency and Molecular Characteristics of Mismatch Repair-deficient Status among Multiple Synchronous Colorectal Cancers
Objectives: Mismatch repair (MMR)-deficient (dMMR) colorectal cancer (CRC) have been largely categorized into three subtypes: MLH1-methylated, Lynch syndrome (LS)-associated, and Lynch-like syndrome (LLS)-associated. No studies have examined the prevalence and subtypes of synchronously diagnosed dMM...
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| Format: | Article |
| Language: | English |
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The Japan Society of Coloproctology
2025-01-01
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| Series: | Journal of the Anus, Rectum and Colon |
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| Online Access: | https://www.jstage.jst.go.jp/article/jarc/9/1/9_2024-092/_pdf/-char/en |
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| _version_ | 1832584939969708032 |
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| author | Kenichi Chikatani Noriyasu Chika Noriko Tanabe Yoshiko Mori Okihide Suzuki Takatoshi Matsuyama Keiichiro Ishibashi Hidetaka Eguchi Yasushi Okazaki Tatsuro Yamaguchi Hideyuki Ishida |
| author_facet | Kenichi Chikatani Noriyasu Chika Noriko Tanabe Yoshiko Mori Okihide Suzuki Takatoshi Matsuyama Keiichiro Ishibashi Hidetaka Eguchi Yasushi Okazaki Tatsuro Yamaguchi Hideyuki Ishida |
| author_sort | Kenichi Chikatani |
| collection | DOAJ |
| description | Objectives: Mismatch repair (MMR)-deficient (dMMR) colorectal cancer (CRC) have been largely categorized into three subtypes: MLH1-methylated, Lynch syndrome (LS)-associated, and Lynch-like syndrome (LLS)-associated. No studies have examined the prevalence and subtypes of synchronously diagnosed dMMR CRCs in detail. Therefore, this study aimed to examine the frequency and molecular characteristics of the dMMR status among multiple synchronous CRCs to clarify the clinical significance of identifying patients with such tumors.
Methods: Immunohistochemistry (IHC) of MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed for surgically and endoscopically resected (in conjunction with surgical resection) lesions from consecutive patients with initially diagnosed multiple synchronous CRCs between July 2014 and June 2020. When necessary, MLH1-methylation analysis and testing of germline and somatic MMR genes were performed.
Results: In total, 133 patients (33 females) had 309 lesions. The combinations of synchronous tumor sites were the left-sided colon/rectum only (n=67, 50.4%), both the right-sided colon and left-sided colon/rectum (n=42, 31.6%), and the right-sided colon only (n=24, 18.0%). IHC showed a loss of expression of at least one MMR protein in 10 (7.5%) of 133 patients and 17 (5.5%) of 309 lesions. Molecular analysis revealed that these 10 patients were categorized as having MLH1-methylated (n=5, 3.8% of all patients), LS-associated (n=4, 3.0%), or LLS-associated (n=1, 0.8%) CRC.
Conclusions: Our data will be useful for genetic counseling in patients with synchronous CRCs suspected of having LS. Screening for LS using IHC for MMR proteins in individuals with multiple synchronous CRCs is an effective approach. |
| format | Article |
| id | doaj-art-8b4e8681ba5e46fd8b4eae22a19273cf |
| institution | Kabale University |
| issn | 2432-3853 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | The Japan Society of Coloproctology |
| record_format | Article |
| series | Journal of the Anus, Rectum and Colon |
| spelling | doaj-art-8b4e8681ba5e46fd8b4eae22a19273cf2025-01-27T10:02:40ZengThe Japan Society of ColoproctologyJournal of the Anus, Rectum and Colon2432-38532025-01-019114515510.23922/jarc.2024-0922024-092Frequency and Molecular Characteristics of Mismatch Repair-deficient Status among Multiple Synchronous Colorectal CancersKenichi Chikatani0Noriyasu Chika1Noriko Tanabe2Yoshiko Mori3Okihide Suzuki4Takatoshi Matsuyama5Keiichiro Ishibashi6Hidetaka Eguchi7Yasushi Okazaki8Tatsuro Yamaguchi9Hideyuki Ishida10Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityDepartment of Clinical Genetics, Saitama Medical Center, Saitama Medical UniversityDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Juntendo University Graduate School of MedicineDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Juntendo University Graduate School of MedicineDepartment of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityObjectives: Mismatch repair (MMR)-deficient (dMMR) colorectal cancer (CRC) have been largely categorized into three subtypes: MLH1-methylated, Lynch syndrome (LS)-associated, and Lynch-like syndrome (LLS)-associated. No studies have examined the prevalence and subtypes of synchronously diagnosed dMMR CRCs in detail. Therefore, this study aimed to examine the frequency and molecular characteristics of the dMMR status among multiple synchronous CRCs to clarify the clinical significance of identifying patients with such tumors. Methods: Immunohistochemistry (IHC) of MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed for surgically and endoscopically resected (in conjunction with surgical resection) lesions from consecutive patients with initially diagnosed multiple synchronous CRCs between July 2014 and June 2020. When necessary, MLH1-methylation analysis and testing of germline and somatic MMR genes were performed. Results: In total, 133 patients (33 females) had 309 lesions. The combinations of synchronous tumor sites were the left-sided colon/rectum only (n=67, 50.4%), both the right-sided colon and left-sided colon/rectum (n=42, 31.6%), and the right-sided colon only (n=24, 18.0%). IHC showed a loss of expression of at least one MMR protein in 10 (7.5%) of 133 patients and 17 (5.5%) of 309 lesions. Molecular analysis revealed that these 10 patients were categorized as having MLH1-methylated (n=5, 3.8% of all patients), LS-associated (n=4, 3.0%), or LLS-associated (n=1, 0.8%) CRC. Conclusions: Our data will be useful for genetic counseling in patients with synchronous CRCs suspected of having LS. Screening for LS using IHC for MMR proteins in individuals with multiple synchronous CRCs is an effective approach.https://www.jstage.jst.go.jp/article/jarc/9/1/9_2024-092/_pdf/-char/enlynch syndromelynch-like syndromemismatch repair-deficientcolorectal cancersynchronous colorectal cancer |
| spellingShingle | Kenichi Chikatani Noriyasu Chika Noriko Tanabe Yoshiko Mori Okihide Suzuki Takatoshi Matsuyama Keiichiro Ishibashi Hidetaka Eguchi Yasushi Okazaki Tatsuro Yamaguchi Hideyuki Ishida Frequency and Molecular Characteristics of Mismatch Repair-deficient Status among Multiple Synchronous Colorectal Cancers Journal of the Anus, Rectum and Colon lynch syndrome lynch-like syndrome mismatch repair-deficient colorectal cancer synchronous colorectal cancer |
| title | Frequency and Molecular Characteristics of Mismatch Repair-deficient Status among Multiple Synchronous Colorectal Cancers |
| title_full | Frequency and Molecular Characteristics of Mismatch Repair-deficient Status among Multiple Synchronous Colorectal Cancers |
| title_fullStr | Frequency and Molecular Characteristics of Mismatch Repair-deficient Status among Multiple Synchronous Colorectal Cancers |
| title_full_unstemmed | Frequency and Molecular Characteristics of Mismatch Repair-deficient Status among Multiple Synchronous Colorectal Cancers |
| title_short | Frequency and Molecular Characteristics of Mismatch Repair-deficient Status among Multiple Synchronous Colorectal Cancers |
| title_sort | frequency and molecular characteristics of mismatch repair deficient status among multiple synchronous colorectal cancers |
| topic | lynch syndrome lynch-like syndrome mismatch repair-deficient colorectal cancer synchronous colorectal cancer |
| url | https://www.jstage.jst.go.jp/article/jarc/9/1/9_2024-092/_pdf/-char/en |
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