Molecular analysis of colorectal cancers suggests a high frequency of lynch syndrome in Indonesia

Susanti, Susanti and Wibowo, Satrio and Akbariani, Gilang and Yoshuantari, Naomi and Heriyanto, Didik Setyo and Ridwanuloh, Asep Muhamad and Hariyatun, Hariyatun and Handaya, Adeodatus Yuda and Kurnianda, Johan and Hutajulu, Susanna Hilda and Ilyas, Mohammad (2021) Molecular analysis of colorectal cancers suggests a high frequency of lynch syndrome in Indonesia. Cancers, 13 (24). ISSN 20726694

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Abstract

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 (NLyST) was used in this project. NLyST 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, p = 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 (n = 227) was comparable (p = 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 (p < 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95 CI: 1.72–11.2; p = 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type: Article
Additional Information: Cited by: 5; All Open Access, Gold Open Access, Green Open Access
Uncontrolled Keywords: adult; Article; cancer grading; cancer patient; cancer staging; capillary electrophoresis; colorectal cancer; female; follow up; gene mutation; genetic modification; high resolution melting analysis; histology; human; human tissue; Indonesia; Indonesian; Lynch syndrome; major clinical study; male; middle aged; molecular pathology; overall survival; promoter region; Sanger sequencing
Subjects: R Medicine > RB Pathology
Divisions: Faculty of Medicine, Public Health and Nursing > Biomedical Sciences
Depositing User: Sri JUNANDI
Date Deposited: 28 Sep 2024 05:58
Last Modified: 28 Sep 2024 05:58
URI: https://ir.lib.ugm.ac.id/id/eprint/4463

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