Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia
There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described...
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MDPI AG
2021-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/24/6245 |
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| author | Susanti Susanti Satrio Wibowo Gilang Akbariani Naomi Yoshuantari Didik Setyo Heriyanto Asep Muhamad Ridwanuloh Hariyatun Hariyatun Adeodatus Yuda Handaya Johan Kurnianda Susanna Hilda Hutajulu Mohammad Ilyas |
| author_facet | Susanti Susanti Satrio Wibowo Gilang Akbariani Naomi Yoshuantari Didik Setyo Heriyanto Asep Muhamad Ridwanuloh Hariyatun Hariyatun Adeodatus Yuda Handaya Johan Kurnianda Susanna Hilda Hutajulu Mohammad Ilyas |
| author_sort | Susanti Susanti |
| collection | DOAJ |
| description | There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016–2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all—186/197 (99.45%)—MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as “Probable Lynch” (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%, <i>p</i> = 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both “Probable Lynch” and non-LS (sporadic) groups (<i>n</i> = 227) was comparable (<i>p</i> = 0.59), with follow up period of 0–1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (<i>p</i> < 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72–11.2; <i>p</i> = 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West. |
| first_indexed | 2024-03-10T04:32:10Z |
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| id | doaj.art-d2747bd3188e4a028fed620ae23a022b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:32:10Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d2747bd3188e4a028fed620ae23a022b2023-11-23T04:05:51ZengMDPI AGCancers2072-66942021-12-011324624510.3390/cancers13246245Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in IndonesiaSusanti Susanti0Satrio Wibowo1Gilang Akbariani2Naomi Yoshuantari3Didik Setyo Heriyanto4Asep Muhamad Ridwanuloh5Hariyatun Hariyatun6Adeodatus Yuda Handaya7Johan Kurnianda8Susanna Hilda Hutajulu9Mohammad Ilyas10Molecular Pathology Research Group, Academic Unit of Translational Medical Science, Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham NG72UH, UKPathGen Diagnostik Teknologi, Center for Innovation and Utilization of Science and Technology, National Research and Innovation Agency (Badan Riset dan Inovasi Nasional/BRIN), Bogor 16911, IndonesiaPathGen Diagnostik Teknologi, Center for Innovation and Utilization of Science and Technology, National Research and Innovation Agency (Badan Riset dan Inovasi Nasional/BRIN), Bogor 16911, IndonesiaDepartment of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito General Hospital, Yogyakarta 55281, IndonesiaDepartment of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito General Hospital, Yogyakarta 55281, IndonesiaResearch Center for Biotechnology, National Research and Innovation Agency (BRIN), Bogor 16911, IndonesiaResearch Center for Biotechnology, National Research and Innovation Agency (BRIN), Bogor 16911, IndonesiaDivision of Digestive Surgeon, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito General Hospital, Yogyakarta 55281, IndonesiaDivision of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito General Hospital, Yogyakarta 55281, IndonesiaDivision of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito General Hospital, Yogyakarta 55281, IndonesiaMolecular Pathology Research Group, Academic Unit of Translational Medical Science, Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham NG72UH, UKThere is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016–2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all—186/197 (99.45%)—MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as “Probable Lynch” (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%, <i>p</i> = 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both “Probable Lynch” and non-LS (sporadic) groups (<i>n</i> = 227) was comparable (<i>p</i> = 0.59), with follow up period of 0–1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (<i>p</i> < 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72–11.2; <i>p</i> = 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West.https://www.mdpi.com/2072-6694/13/24/6245microsatellite instability (MSI)BRAF mutationMLH1 promoter methylationhigh Resolution melting (HRM)early onset colorectal cancer (EOCRC) |
| spellingShingle | Susanti Susanti Satrio Wibowo Gilang Akbariani Naomi Yoshuantari Didik Setyo Heriyanto Asep Muhamad Ridwanuloh Hariyatun Hariyatun Adeodatus Yuda Handaya Johan Kurnianda Susanna Hilda Hutajulu Mohammad Ilyas Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia Cancers microsatellite instability (MSI) BRAF mutation MLH1 promoter methylation high Resolution melting (HRM) early onset colorectal cancer (EOCRC) |
| title | Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia |
| title_full | Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia |
| title_fullStr | Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia |
| title_full_unstemmed | Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia |
| title_short | Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia |
| title_sort | molecular analysis of colorectal cancers suggests a high frequency of lynch syndrome in indonesia |
| topic | microsatellite instability (MSI) BRAF mutation MLH1 promoter methylation high Resolution melting (HRM) early onset colorectal cancer (EOCRC) |
| url | https://www.mdpi.com/2072-6694/13/24/6245 |
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