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  1. Microsatellite Instability and Altered Expressions of MLH1 and MSH2 in Gastric Cancer
    Haron NH, Mohamad Hanif EA, Abdul Manaf MR, Yaakub JA, Harun R, Mohamed R, et al.
    Asian Pac J Cancer Prev, 2019 Feb 26;20(2):509-517.
    PMID: 30803214
    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.
    Matched MeSH terms: MutS Homolog 2 Protein/metabolism*
  2. Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening
    Wan Juhari WK, Wan Abdul Rahman WF, Mohd Sidek AS, Abu Hassan MR, Ahmad Amin Noordin KB, Zakaria AD, et al.
    Asian Pac J Cancer Prev, 2015;16(9):3767-71.
    PMID: 25987035
    BACKGROUND: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry.

    MATERIALS AND METHODS: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.

    RESULTS: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively.

    CONCLUSIONS: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

    Matched MeSH terms: MutS Homolog 2 Protein/metabolism
  3. Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma
    Kaur G, Masoud A, Raihan N, Radzi M, Khamizar W, Kam LS
    Indian J Med Res, 2011 Aug;134:186-92.
    PMID: 21911971
    DNA mismatch repair gene (MMR) abnormalities are seen in 95 per cent of hereditary nonpolyposis colorectal cancer (HNPCC) and 10-15 per cent of sporadic colorectal cancers. There are no data on MMR abnormalities in Malaysian colorectal cancer patients. This study was aimed to determine the frequency of abnormal MMR gene protein expression in colorectal carcinoma in Northern Peninsular Malaysia using immunohistochemistry.
    Matched MeSH terms: MutS Homolog 2 Protein/metabolism*
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