Deficient DNA mismatch repair is associated with favorable prognosis in Thai patients with sporadic colorectal cancer

Korphaisarn, Krittiya; Pongpaibul, Ananya; Limwongse, Chanin; Roothumnong, Ekkapong; Klaisuban, Wipawi; Nimmannit, Akarin; Jinawath, Artit; Akewanlop, Charuwan

doi:10.3748/wjg.v21.i3.926

Cited by 26 publications

(18 citation statements)

References 25 publications

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“…The distribution of primary site of MMR-D cancers enrolled in the study is rather similar to our cohort in which colorectal and gastric cancers showed high prevalence of MSI-H. The overall prevalence of MSI-H CRCs in our patients (11%, n=118) is slightly lower than that (15%, n= 211) reported in Thai population by Korphaisarn et al 11 Varied study populations and sample size may have resulted in the differences. While the previous Thai series included all stages of CRCs, all of our patients are presumably advanced stage and MSI testing was likely requested for immunotherapy.…”

Section: Discussionsupporting

confidence: 78%

Increasing Demand for MSI Testing and Prevalence of MSI-H Cancers in Thai Patients: Experience at Chulalongkorn GenePRO Center.

Laohawetwanit¹,

Boonkasem²,

Thongsawang³

et al. 2019

bkkmedj

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NA mismatch repair (MMR) is necessary for all organisms in order to maintain DNA integrity. Loss of expression of one of the MMR proteins results in several sporadic and inherited human cancers of various organs such as colon, rectum, stomach, uterus, and ovary. 1 Microsatellite instability (MSI) was shown to be associated with some cancer types, better survival and/or outcome, and reduced likelihood of distant metastases and susceptible to chemotherapy. 2-4 Either immunohistochemical study showing loss of MMR proteins expression or PCR-based assay for microsatellite instability can be used to evaluate the MMR status of cancer tissue. 5 Colorectal cancer (CRC), particularly those occurring in the setting of Lynch syndrome, is the prototype of malignancy with microsatellite instability. MMR status has extensively been studied in CRCs 3,4,6-10 and although deficiency of DNA mismatch repair was reported in 15% of Thai patients with sporadic CRCs, 11 MSI testing is not routinely performed as part of the clinical practice in Thailand. Immunotherapy has played a significant role in cancer treatment and recent clinical studies have suggested that mismatch repair-deficient cancers, regardless of tissue origin, are susceptible to immune-checkpoint inhibitors e.g. PD-1 blockade. 12,13 In May 2017, the US Food and Drug Administration (FDA) granted an accelerated approval to pembrolizumab, an antibody to the PD-1 receptor, as an alternative Abstract RATIONALE: Loss of DNA mismatch repair function has long been known in various malignancies, particularly colorectal cancer. However, microsatellite instability (MSI) testing was rarely requested in Thailand. Recently, the US Food and Drug Administration (FDA) has approved pembrolizumab, an antibody to PD-1 receptor, as an alternative treatment for high MSI (MSI-H) and/or MMR (mismatch repair)-deficient solid tumors. We report our recent observation on MSI testing in Thailand. MATERIALS AND METHODS: Data was collected from Chulalongkorn GenePRO Center, Faculty of Medicine, Chulalongkorn University, during July 2013 and July 2017. MSI testing was performed, using 5 microsatellite markers (BAT-25, BAT-26, D2S123, D5S346 and D17S250). The number, source, and result of samples underwent MSI assay were analyzed. RESULTS: Requests for MSI testing have increased significantly in recent years. The shift started in 2015 when the MMR status was found to predict clinical benefit with the immune checkpoint blockade. There were 118 (75.2%) colorectal, 11 (7%) gastric, and 28 (17.8%) other cancers tested. MSI-H, MSI-L, and microsatellite stable (MSS) tumors were detected in 18 (11.5%), 11 (7%), and 128 (81.5%) patients, respectively. Of the 18 MSI-H cancers; 13 (72.2%), 4 (22.2%), and 1 (5.6%) were colorectal, gastric, and gynecologic malignancy, respectively. BAT25 and BAT26 markers were unstable in all MSI-H tumors. CONCLUSION: We have experienced increasing demand for MSI testing in Thai patients at Chulalongkorn GenePRO Center. Colorectal cancers were most frequently tested, and accounted ...

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Section: Discussionsupporting

confidence: 78%

Increasing Demand for MSI Testing and Prevalence of MSI-H Cancers in Thai Patients: Experience at Chulalongkorn GenePRO Center.

Laohawetwanit¹,

Boonkasem²,

Thongsawang³

et al. 2019

bkkmedj

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“…An additional 65 studies contained relevant data for KRAS, NRAS, or BRAF mutation status and tumor sidedness but did not report data specific to the mCRC population or data for mutation status by tumor sidedness. We contacted the authors of these studies for data availability and received relevant data from five studies . A total of 44 studies were therefore included in the narrative review and meta‐analyses.…”

Section: Resultsmentioning

confidence: 99%

Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta‐analysis

et al. 2019

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Studies have shown that the prevalence of RAS and BRAF mutations may differ by tumor sidedness among metastatic colorectal cancer (mCRC) patients. Both mutation status and tumor sidedness may impact survival and disease progression and RAS mutation status has been shown to predict response to anti-epidermal growth factor receptor (EGFR) therapy. A systematic literature review and meta-analysis were conducted to estimate the pooled prevalence of RAS and BRAF mutations by tumor sidedness in studies of mCRC patients. Forty-four studies comprising 15 981 mCRC patients tested for RAS and/or BRAF mutations were included in the meta-analyses. The prevalence of RAS mutations differed significantly by tumor side (32.4% among left-sided tumors, 41.3% among right-sided tumors; P = .017), as did the prevalence of KRAS mutations (35.8% among left-sided tumors, 46.3% among right-sided tumors; P < .0001) and BRAF mutations (4.3% among left-sided tumors, 16.3% among right-sided tumors; P < .0001). Among right-sided tumors, the prevalence of RAS and KRAS mutations varied significantly by study design, with higher prevalence among observational studies than clinical trials, and there was significant variation by study location for the prevalence of KRAS mutations in left-sided tumors and the prevalence of BRAF mutations in right-sided tumors. These results help to better characterize the mCRC population to better inform clinicians and researchers. Few of the included studies reported overall or progression-free survival (PFS) by both tumor sidedness and mutation status. As both of these factors may have prognostic impact, future studies should consider evaluating survival by these variables. K E Y W O R D S BRAF, KRAS, metastatic colorectal cancer, RAS, tumor sidedness | 1045 BYLSMA et AL. ORCID Lauren C. Bylsmahttps://orcid.

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“…Tumor phenotypes may vary with process of tumor infiltration and metastasis[30, 31]. For instance, mismatch repair deficiency (MMR) was associated with early-stage, non-metastatic CRC[32]. Also, expression of MHC-I has been found to decrease with tumor growth and invasion in CRC, with corresponding decreases in survival[33].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Differently Located Colorectal Cancers Support Proximal and Distal Classification: A Population-Based Study of 57,847 Patients

Jiao

Du²,

et al. 2016

PLoS ONE

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BackgroundIt has been suggested that colorectal cancer be regarded as several subgroups defined according to tumor location rather than as a single entity. The current study aimed to identify the most useful method for grouping colorectal cancer by tumor location according to both baseline and survival characteristics.MethodsCases of pathologically confirmed colorectal adenocarcinoma diagnosed from 2000 to 2012 were identified from the Surveillance, Epidemiology, and End Results database and categorized into three groups: right colon cancer (RCC), left colon cancer (LCC), and rectal cancer (ReC). Adjusted hazard ratios for known predictors of disease-specific survival (DSS) in colorectal cancer were obtained using a Cox proportional hazards regression model.ResultsThe study included 57847 patients: 43.5% with RCC, 37.7% with LCC, and 18.8% with ReC. Compared with LCC and ReC, RCC was more likely to affect old patients and women, and to be at advanced stage, poorly differentiated or un-differentiated, and mucinous. Patients with LCC or ReC had better DSS than those with RCC in subgroups including stage III or IV disease, age ≤70 years and non-mucinous adenocarcinoma. Conversely, patients with LCC or ReC had worse DSS than those with RCC in subgroups including age ˃70 years and mucinous adenocarcinoma.ConclusionsRCC differed from both LCC and ReC in several clinicopathologic characteristics and in DSS. It seems reasonable to group colorectal cancer into right-sided (i.e., proximal) and left-sided (i.e., distal) ones.

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Deficient DNA mismatch repair is associated with favorable prognosis in Thai patients with sporadic colorectal cancer

Abstract: The prevalence of dMMR and BRAF V600E in Thai sporadic CRC patients was 15% and 11%, respectively. The dMMR phenotype was associated with a favorable outcome.

Cited by 26 publications

References 25 publications

Increasing Demand for MSI Testing and Prevalence of MSI-H Cancers in Thai Patients: Experience at Chulalongkorn GenePRO Center.

Increasing Demand for MSI Testing and Prevalence of MSI-H Cancers in Thai Patients: Experience at Chulalongkorn GenePRO Center.

Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta‐analysis

Characteristics of Differently Located Colorectal Cancers Support Proximal and Distal Classification: A Population-Based Study of 57,847 Patients

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