Microsatellite Instability and Altered Expressions of MLH1 and MSH2 in Gastric Cancer

Document Type : Research Articles

Authors

1 Department of Pathology, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia.

2 UKM Medical Molecular Biology Institute (UMBI), University Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur.

3 Department of Community Health, University Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia.

4 General Surgery, KPJ Ampang Puteri Specialist Hospital, No. 1 Jalan Mamanda 9, Taman Dato Ahmad Razali, 68000 Ampang, Selangor Darul Ehsan, Malaysia.

Abstract

Introduction: Microsatellite instability (MSI) is a hallmark of defective DNA mismatch repair (MMR) of genes
especially MLH1 and MSH2. It is frequently involved in the carcinogenesis of various tumours including gastric
cancer (GC). However, MSI in GCs have not been reported in Malaysia before. Objective: This study was conducted
to determine the microsatellite instability (MSI) status in gastric cancer by microsatellite analysis, sequencing, its
association with MLH1 and MSH2 protein expression and H.pylori infection by immunohistochemistry. Method:
A total of 60 gastric cancer cases were retrieved. DNA was extracted from paired normal and tumour tissues while
MLH1 and MSH2 protein expression as well as H. pylori status were determined by IHC staining. For microsatellite
analysis, polymerase chain reaction (PCR) was performed for paired tissue samples using a panel of five microsatellite
markers. MSI-positive results were subjected for DNA sequencing to assess mutations in the MLH1 and MSH2 genes.
Results: Microsatellite analysis identified ten MSI positive cases (16.7%), out of which only six cases (10.3%) showed
absence of MLH1 (n=3) or MSH2 (n=3) protein expression by IHC. The most frequent microsatellite marker in MSI
positive cases was BAT26 (90%). Nine of ten MSI positive cases were intestinal type with one diffuse and all were
located distally. H. pylori infection was detected in 13 of 60 cases (21.7%) including in three MSI positive cases. All
these results however were not statistically significant. Our sequencing data displayed novel mutations. However these
data were not statistically correlated with expression levels of MLH1 and MSH2 proteins by IHC. This may be due
to small sample size to detect small or moderately sized effects. Conclusion: The frequency of MSI in this study was
comparable with published results. Determination of affected MMR genes by more than two antibodies may increase
the sensitivity of IHC to that of MSI analysis.

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Main Subjects

Asian Pacific Journal of Cancer Prevention
Volume 20, Issue 2
February 2019
Pages 509-517

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History

  • Receive Date: 02 June 2018
  • Revise Date: 05 January 2019
  • Accept Date: 30 January 2019

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