West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter. Asian Pacific Journal of Cancer Prevention 1513-7368 20 2 2019 02 01 Microsatellite Instability and Altered Expressions of MLH1 and MSH2 in Gastric Cancer 509 517 82533 10.31557/APJCP.2019.20.2.509 EN Nor Hasyimah Haron Department of Pathology, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia. UKM Medical Molecular Biology Institute (UMBI), University Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur. 0000-0002-2069-5175 Ezanee Azlina Mohamad Hanif UKM Medical Molecular Biology Institute (UMBI), University Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur. 0000-0002-7386-7727 Mohd Rizal Abdul Manaf Department of Community Health, University Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia. Jasmi Ali Yaakub General Surgery, KPJ Ampang Puteri Specialist Hospital, No. 1 Jalan Mamanda 9, Taman Dato Ahmad Razali, 68000 Ampang, Selangor Darul Ehsan, Malaysia. Roslan Harun UKM Medical Molecular Biology Institute (UMBI), University Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur. Ramelah Mohamed UKM Medical Molecular Biology Institute (UMBI), University Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur. Isa Mohamed Rose Department of Pathology, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia. Journal Article 2018 06 02 Introduction: Microsatellite instability (MSI) is a hallmark of defective DNA mismatch repair (MMR) of genes<br />especially MLH1 and MSH2. It is frequently involved in the carcinogenesis of various tumours including gastric<br />cancer (GC). However, MSI in GCs have not been reported in Malaysia before. Objective: This study was conducted<br />to determine the microsatellite instability (MSI) status in gastric cancer by microsatellite analysis, sequencing, its<br />association with MLH1 and MSH2 protein expression and H.pylori infection by immunohistochemistry. Method:<br />A total of 60 gastric cancer cases were retrieved. DNA was extracted from paired normal and tumour tissues while<br />MLH1 and MSH2 protein expression as well as H. pylori status were determined by IHC staining. For microsatellite<br />analysis, polymerase chain reaction (PCR) was performed for paired tissue samples using a panel of five microsatellite<br />markers. MSI-positive results were subjected for DNA sequencing to assess mutations in the MLH1 and MSH2 genes.<br />Results: Microsatellite analysis identified ten MSI positive cases (16.7%), out of which only six cases (10.3%) showed<br />absence of MLH1 (n=3) or MSH2 (n=3) protein expression by IHC. The most frequent microsatellite marker in MSI<br />positive cases was BAT26 (90%). Nine of ten MSI positive cases were intestinal type with one diffuse and all were<br />located distally. H. pylori infection was detected in 13 of 60 cases (21.7%) including in three MSI positive cases. All<br />these results however were not statistically significant. Our sequencing data displayed novel mutations. However these<br />data were not statistically correlated with expression levels of MLH1 and MSH2 proteins by IHC. This may be due<br />to small sample size to detect small or moderately sized effects. Conclusion: The frequency of MSI in this study was<br />comparable with published results. Determination of affected MMR genes by more than two antibodies may increase<br />the sensitivity of IHC to that of MSI analysis. https://journal.waocp.org/article_82533_a738a47e97466f0f40d0ceaab991f436.pdf