Microsatellite instability of gastric cancer and precancerous lesions.
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ABSTRACT:
SUBMITTER: Li B
PROVIDER: S-EPMC4723891 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
Microsatellite instability of gastric cancer and precancerous lesions.
Li Bing B Liu Hong-Yi HY Guo Shao-Hua SH Sun Peng P Gong Fang-Ming FM Jia Bao-Qing BQ
International journal of clinical and experimental medicine 20151115 11
<h4>Objective</h4>To investigate whether microsatellite instability (MSI) of gastric cancer and precancerous lesions were existed and its effect.<h4>Methods</h4>Laser microdissection was used. Gastric, intestinal metaplasia, dysplasia and normal mucosa were collected respectively. Five microsatellite loci were selected and MSI was detected by denaturing high-performance liquid chromatography.<h4>Results</h4>In the five microsatellite loci REF-positive phenotype, intestinal metaplasia MSI was 20. ...[more]
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Project description:AimTo investigate the microsatellite instability (MSI) in cancer and pre-cancerous lesions of the stomach and its mechanisms underlying the development of gastric cancer.MethodsThirty-six gastric cancer samples were obtained from patients undergoing surgery. Forty-one gastric mucosa samples with dysplasia and 51 with intestinal metaplasia (IM) were obtained from patients with chronic gastritis undergoing gastro-endoscopy. Genomic DNA was extracted from the samples. Silver staining single strand conformation polymorphis-polymerize chain reaction (SSCP-PCR) was used to screen MSI markers at 5 loci (Bat-25, Bat-26, D5S346, D17S250, and D2S123) in fresh tissues and formalin-fixed, paraffin-embedded samples and their corresponding normal gastric mucosa.ResultsThe abnormal shifting of the single-strand DNA (MSI) was identified in 21 out of 36 (58.3%) gastric cancers. Seven cases showed high-level MSI (two or more loci altered) and 14 showed low-level MSI (one locus altered). Gastric cancer with MSI had a tendency to be located in the distal stomach. MSI was also detected in 11 out of 41 (26.8%) dysplasia samples and in 9 of 51 (17.6%) IM samples respectively. Three cases of dysplasia and one case of IM showed high-level MSI. Eight cases of dysplasia and 8 cases of IM displayed low-level MSI. MIS in IM was found only in moderate or severe-grade IM. No association was detected between MSI and dysplasia grade.ConclusionAccumulation of MSI in dysplasia and intestinal metaplasia of gastric mucosa may be an early molecular event during gastric carcinogenesis and may contribute to the acquisition of transformed cell phenotype and the development of gastric cancer.
| S-EPMC4398747 | biostudies-literature
Project description:Gastric cancer (GC) remains a leading cause of cancer mortality worldwide. Genetic factors are implicated, including DNA mismatch repair (MMR) deficiency manifested as tumor microsatellite instability (MSI). However, a standardized panel of markers and a definition of low-versus-high level MSI in GC are lacking. We examined a population-based cohort of early onset (<or=50 yrs) gastric cancer. We identified 211 cases of early onset gastric cancer in Central-East Ontario from 1989 to 1993, with archival material available for 139 cases. Testing included a six-mononucleotide marker panel and a three-MMR immunohistochemical panel. Overall, 30% (41 of 139) of GC were MSI+, with allelic shifts at one to eight markers. An unexpected discordance between the BAT-25, BAT-26, and BAT-40 markers was observed in the MSI+ cases. Six cases showing multiple loci instability (>or=3 markers MSI+/MSI-high) demonstrated MMR protein deficiency. Three novel hMLH1 mutations (two germline frameshift and one somatic nonsense) were also found. The only significant clinicopathological associations were increased tumor size in MSI+ cases (P=0.04) and Lauren histotype (P=0.006) and tumor grade (P=0.007) in MSI-high cases. Tumor size, location, depth, nodal status, and Ming subtype were significant prognostic variables. Therefore, we propose a new definition of high-level MSI based on unifying characteristics of instability of more than or equal to three of six mononucleotide markers and loss of MMR protein expression.
| S-EPMC1888489 | biostudies-literature
Project description:PurposeMicrosatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated.Material and methodsThis study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers.ResultsOf 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040).ConclusionMSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.
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Project description:AimTo observe the curative effect of Weiansan (WAS) on gastric precancerous lesions (GPL) and H pylori elimination.MethodsSeventy-six patients with GPL were randomly divided into two groups: WAS group (n = 42) and Weifuchun (WFC) group (n = 34). The patients in the WAS group were administered 5 g WAS 3 times a day, and the patients in the WFC group took WFC (4 tablets) 3 times a day. To monitor inflammation of gastric mucosa, degree of glandular atrophy (GA), intestinal metaplasia (IM) and dysplasia, and H pylori infection, all patients underwent gastroscopy and biopsy with pathological examination before and after treatment. Fifty male Sprague-Dawley (SD) rats were used in animal experiments. Of these, 10 served as the control group (n = 10), 40 were given ranitidine combined with N-methyl-N(1)-nitro-N-nitrosoguanidine (MNNG) for 12 wk and divided into 4 groups randomly: model group (n = 10), high-dose WAS group (n = 10), low-dose WAS group (n = 10) and WFC group (n = 10). Twelve weeks later, all rats were killed and a 2 cm multiply 1 cm tissue was taken from the lesser curvature of the gastric antrum. H pylori infection was determined by the fast urease method.ResultsThe curative effect in WAS groups was similar to that in WFC groups. There was no statistical difference in degree of GA, IM and dysplasia between WAS and WFC groups. The rate of H pylori infection in the model group (positive/negative: 9/1) was significantly higher than that in the control group (positive/negative: 1/9) (P < 0.01). H pylori elimination in the high-dose WAS group (positive/negative: 4/6) and low-dose WAS group (positive/negative: 6/4) was similar to that in the WFC group (positive/negative: 4/6) (P > 0.05).ConclusionWAS improves clinical symptoms by suppressing GA, IM and dysplasia and eliminating H pylori.
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Project description:ObjectiveTo detect the expression of the Oncostatin M (OSM) gene and encoded protein in the mucosal epithelium of chronic gastritis, intestinal metaplasia (IM), low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), early gastric cancer (EGC), and advanced gastric cancer (AGC) samples and to explore the correlation and clinicopathological significance of OSM expression in the process of gastric carcinogenesis.MethodsThe expression levels of OSM in chronic gastritis, IM, LGIN, HGIN, EGC, and AGC samples were detected by gene chip, real-time quantitative PCR, and immunohistochemical methods. The expression levels of OSM in the gastric mucosa were analyzed, and its correlation with clinical pathology was studied.ResultsThe expression level of OSM in gastric HGIN and EGC tissues was significantly higher than that in LGIN tissues based on expression profiling (P < 0.001). The expression of the OSM gene in EGC was higher than that in HGIN (unpaired t test, P < 0.05) and LGIN (unpaired t test, P < 0.01) by qPCR. The expression of OSM in LGIN was significantly lower than that in HGIN (P = 0.008) and EGC (P = 0.044) by immunohistochemical staining. The expression of OSM in HGIN tissues was significantly higher than that in AGC (P = 0.007).ConclusionAlterations in the expression of the OSM gene may be involved in the malignant transformation of the gastric mucosal epithelium. Because of the significant difference in the cancerization rate and clinical management between LGIN and HGIN, the difference in the staining intensity of OSM between LGIN and HGIN may be one of the early markers of gastric intraepithelial neoplasia.
| S-EPMC6913316 | biostudies-literature
Project description:Although recent studies have suggested that tooth loss is positively related to the risk of gastric non-cardia cancer, the underlying oral health conditions potentially responsible for the association remain unknown. We investigated whether clinical and behavioral measures of oral health are associated with the risk of gastric precancerous lesions. We conducted a cross-sectional study of 131 patients undergoing upper gastrointestinal endoscopy. Cases were defined as those with gastric precancerous lesions including intestinal metaplasia or chronic atrophic gastritis on the basis of standard biopsy review. A validated structured questionnaire was administered to obtain information on oral health behaviors. A comprehensive clinical oral health examination was performed on a subset of 91 patients to evaluate for periodontal disease and dental caries experience. A total of 41 (31%) cases of gastric precancerous lesions were identified. Compared with non-cases, cases were significantly more likely to not floss their teeth [odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.09-7.64], adjusting for age, sex, race, body mass index, smoking status, educational attainment and Helicobacter pylori status in serum. Among participants who completed the oral examination, cases (n = 28) were more likely to have a higher percentage of sites with gingival bleeding than non-cases [OR = 2.63, 95% CI: 1.37-5.05 for a standard deviation increase in bleeding sites (equivalent to 19.7%)], independent of potential confounders. Our findings demonstrate that specific oral health conditions and behaviors such as gingival bleeding and tooth flossing are associated with gastric precancerous lesions.
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Project description:OBJECTIVE:We aimed to investigate the association between gastric cancer and microsatellite instability (MSI) in the present study. METHOD:Phenol-chloroform method was employed for DNA extraction from the cancer tissues of 65gastric cancer patients and the dysplasia tissues and normal control tissues of 32 non-gastric cancer patients. The microsatellite loci Bat25, Bat26, D2S123, D5S346 and D17S250 were detected by using PCR-SSCP silver staining technique, and the MSI of the gastric cancer tissues and the precancerous tissues was analyzed. RESULTS:Of 65 gastric cancer cases, MSI was detected in 43 cases, with the detection rate of 66.2%. There were 13 cases showing MSI-H and 30 cases showing MSI-L, accounting for 30.2% and 69.8%, respectively. Among 32 cases of dysplasia tissues, MSI was detected in 10 cases, with the detection rate of 31.3%. Two cases of dysplasia tissues showed MSI-H and 8 cases showed MSI-L, accounting for 20.0% and 80.0%, respectively. CONCLUSION:Gastric cancer patients had a high detection rate of MSI. It is speculated that MSI is another molecular mechanism of carcinogenesis and may serve as a sensitive diagnostic indicator of gastric cancer.
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Project description:Background/aimsThe usefulness of immunohistochemistry to screen for the microsatellite instability (MSI) phenotype in gastric cancer remains unclear. Moreover, the prognostic value of MSI phenotypes in gastric cancer has been debated.MethodsThe clinicopathologic parameters and survival outcomes of 203 MSI-high (MSI-H) and 261 microsatellite-stable (MSS) advanced gastric cancers (AGCs) were compared. Next, we compared the immunohistochemistry results for hMLH1 and hMSH2 with those of a polymerase chain reaction (PCR)-based method. Kaplan-Meier curves and a Cox proportional hazard regression model were used to conduct survival analyses.ResultsThe MSI-H AGCs were correlated with older age (p<0.001), female gender (p=0.018), distal location (p<0.001), larger size (p=0.016), and intestinal type (p<0.001). Multivariate analysis revealed that the MSI-H phenotype was an independent favorable factor that was related to overall survival in patients with AGC (p<0.001). Compared with the PCR-based analysis, immunohistochemistry exhibited high sensitivity (91.1%) and specificity (98.5%) in the detection of MSI phenotypes.ConclusionsMSI-H gastric cancers have distinct clinicopathologic features and better prognoses, which suggests the necessity of MSI analysis in gastric cancer. Immunohistochemistry can be a useful and reliable screening method in the assessment of MSI status in gastric cancer.
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Project description:Objective:The clinical outcomes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer have been attributed to the interplay of virulence factors of Helicobacter pylori (H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. Methods:Chronic gastritis, atrophic gastritis, and intestinal metaplasia specimens were obtained from patients who underwent endoscopy and surgical resection between January 2017 and December 2018; specimens from gastric cancer patients treated between January 2014 and December 2018 were also added. H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of. Results:H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of vacA, babA2, and oipA genes and their association with clinical outcomes. vacA, babA2, and oipA genes and their association with clinical outcomes. P=0.033, OR?=?2.64; 95% CI?=?1.44-4.82, P=0.033, OR?=?2.64; 95% CI?=?1.44-4.82, P=0.033, OR?=?2.64; 95% CI?=?1.44-4.82, H. pylori vacA +/babA2, and oipA genes and their association with clinical outcomes. P=0.033, OR?=?2.64; 95% CI?=?1.44-4.82. Conclusion:In this present study, we reported on the virulence genes of H. pylori infection to reveal their association with increased risk of chronic gastritis, precancerous gastric lesions, and gastric cancer. Precancerous gastric lesions with H. pylori vacA+/babA2+/oipA+ genotype increased the risk of gastric cancer.H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of H. pylori vacA +/babA2, and oipA genes and their association with clinical outcomes.
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Project description:We examined whether colonization of selected oral pathogens is associated with gastric precancerous lesions in a cross-sectional study. A total of 119 participants were included, of which 37 were cases of chronic atrophic gastritis, intestinal metaplasia, or dysplasia. An oral examination was performed to measure periodontal indices. Plaque and saliva samples were tested with real-time quantitative PCR for DNA levels of pathogens related to periodontal disease (Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Actinobacillus actinomycetemcomitans) and dental caries (Streptococcus mutans and S. sobrinus). There were no consistent associations between DNA levels of selected bacterial species and gastric precancerous lesions, although an elevated but non-significant odds ratio (OR) for gastric precancerous lesions was observed in relation to increasing colonization of A. actinomycetemcomitans (OR = 1.36 for one standard deviation increase, 95% Confidence Interval = 0.87-2.12), P. gingivalis (OR = 1.12, 0.67-1.88) and T. denticola (OR = 1.34, 0.83-2.12) measured in plaque. To assess the influence of specific long-term infection, stratified analyses by levels of periodontal indices were conducted. A. actinomycetemcomitans was significantly associated with gastric precancerous lesions (OR = 2.51, 1.13-5.56) among those with ? median of percent tooth sites with PD ? 3 mm, compared with no association among those below the median (OR = 0.86, 0.43-1.72). A significantly stronger relationship was observed between the cumulative bacterial burden score of periodontal disease-related pathogens and gastric precancerous lesions among those with higher versus lower levels of periodontal disease indices (p-values for interactions: 0.03-0.06). Among individuals with periodontal disease, high levels of colonization of periodontal pathogens are associated with an increased risk of gastric precancerous lesions.
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