Differences in biological features of gastric dysplasia, indefinite dysplasia, reactive hyperplasia and discriminant analysis of these lesions

AIM: To investigate the differences in biological features of gastric dysplasia (Dys), indefinite dysplasia (IDys) and reactive hyperplasia (RH) by studying the biomarker alterations in cell proliferation, cell differentiation, cell cycle control and the expression of house-keeping genes, and further to search for markers which could be used in guiding the pathological diagnosis of three lesions. METHODS: Expressions of MUC5AC, MUC6, adenomatous polyposis coli (APC), p53, Ki-67, proliferation cell nuclear antigen (PCNA) and EGFR were studied by immunohistochemistry with a standard Envision technique in formalinfixed and paraffin-embedded specimens from 43 RH, 35 IDys, 35 Dys and 36 intestinal type gastric carcinomas (IGC). In addition, Bayes discriminant analysis was used to investigate the value of markers studied in differential diagnosis of RH, IDys, Dys and IGC. RESULTS: The MUC5AC and MUC6 antigen expressions in RH, IDys, Dys and IGC decreased gradually (MUC5AC:86.04%, 77.14%, 28.57%, 6.67%; MUC6: 65.15%, 54.29%, 20.00%, 25.00%, respectively). The expressions of the two markers had no significant difference between RH and IDys, but were all significantly higher than those ofthe other two lesions (MUC5AC: x2 = 27.607, 38.027 and 17.33, 26.092; MUC6: x2= 16.54, 12.665 and 9.282, 6.737, P＜0.01). There was no significant differencebetween RH and IDys, Dys and IGC in MUC6 expression. The APC gene expression in the four lesions had a similar decreasing tendency (RH 69.76%, IDys 68.57%, Dys39.39%, IGC 22.86%), and it was significantly higher in the first two lesions than in the last two (x2 = 7.011,16.995 and 14.737, 19.817, P＜0.05). The p53 expressionin RH, IDys, Dys and IGC was 6.98%, 20%, 57.14% and 50%, respectively. There was no significant differencebetween RH and IDys or Dys and IGC, but the p53 expression in RH and IDys was significantly lower than that in Dys and IGC (x2 = 7.011, 16.995 and 14.737, 19.817, P＜0.01).The Ki-67 label index was significantly different among four lesions (RH: 0.298±8.92%, IDys: 0.358±9.25%,Dys: 0.498±9.03%, IGC: 0.620±10.8%, P＜0.001). Positive immunostaining of PCNA was though observed in all specimens, significant differences were detected among four lesions (F= 95.318, P＜0.01). In addition, we used Bayes discriminant analysis to investigate molecular pathological classification of the lesions, and obtained the best result with the combination of MUC5AC, Ki-67 and PCNA. The overall rate of correct classification was67.4% (RH), 68.6% (IDys), 70.6% (Dys) and 84.8% (IGC), respectively.CONCLUSION: Dys has neoplastic biological characteristics, while RH and IDys display hyperplastic characteristics. MUC5AC and proliferation-related biomarkers (Ki-67, PCNA) are more specific in distinguishing Dys from RH and IDys.

Risk factors for metachronous gastric carcinoma development after endoscopic resection of gastric dysplasia: Retrospective, single-center study

To determine the gastric adenocarcinoma (GAC) occurrence rate and related factors, we evaluated the follow-up results of patients confirmed to have gastric dysplasia after endoscopic resection (ER). METHODSWe retrospectively analyzed the medical records, endoscopic examination records, endoscopic procedure records, and histological records of 667 cases from 641 patients who were followed-up for at least 12 mo, from among 1273 patients who were conformed to have gastric dysplasia after Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of gastric mucosal lesions between January 2007 and August 2013 at the Chungnam National University Hospital. RESULTSThe mean follow-up period was 33.8 mo, and the median follow-up period was 29 mo (range: 12-87). During the follow-up period, the occurrence of metachronous GAC was 4.0% (27/667). The mean and median interval periods between the occurrence of metachronous GAC and endoscopic treatment of gastric dysplasia were 36.3 and 34 mo, respectively (range: 16-71). The factors related to metachronous GAC occurrence after ER for gastric dysplasia were male sex (5.3% vs 1.0%), open-type atrophic gastritis (9.5% vs 3.4%), intestinal metaplasia (6.8% vs 2.4%), and high-grade dysplasia (HGD; 8.4% vs 3.2%). Among them, male sex [OR: 5.05 (1.18-21.68), P = 0.029], intestinal metaplasia [OR: 2.78 (1.24-6.23), P = 0.013], and HGD [OR: 2.70 (1.16-6.26), P = 0.021] were independent related factors in multivariate analysis. Furthermore, 24 of 27 GAC cases (88.9%) occurred at sites other than the previous resection sites, and 3 (11.1%) occurred at the same site as the previous resection site. CONCLUSIONMale sex, intestinal metaplasia, and HGD were significantly related to the occurrence of metachronous GAC after ER of gastric dysplasia, and most GACs occurred at sites other than the previous resection sites.

Gastric dysplasia may be an independent risk factor of an advanced colorectal neoplasm

AIM: To evaluate the relationship between gastric dysplasia and Helicobacter pylori (H pylori) and the occurrence of colorectal adenoma, and to defi ne the necessity for colonoscopy in patients with gastric dysplasia or H pylori infection.METHODS: From May 2005 to February 2008, 133 patients with established gastric dysplasia by gastroduo-denoscopy (EGD) were additionally investigated by colonoscopy. The authors compared results with those of 213 subjects who underwent both EGD and colonoscopy during the same period at the author’s Health Promotion Center as a control group. H pylori infection was evaluated in both the gastric dysplasia and control groups.RESULTS: The mean age of all 346 study subjects was 54.1 ± 10.5 years, and there were 258 (73%) men and 87 (27%) women. No signif icant difference was found between the H pylori positive and negative subjects in terms of the prevalence of colorectal adenoma and advanced colorectal adenoma (P = 0.261). Patients with gastric dysplasia showed no elevated risk of colorectal adenoma (OR = 0.910, 95% CI: 0.587-1.411, P = 0.738), but had a signif icantly higher risk of having advanced colorectal adenoma (OR = 3.382, 95% CI: 1.700-6.342, P = 0.000).CONCLUSION: The study emphasizes the need for colon surveillance in patients with gastric dysplasia, regardless of H pylori infection.

RESEARCH ON SERUM LEVELS OF RETINOL，α－TOCOPHEROL β－CAROTENE，AND 12 ELEMENTS IN GASTRIC DYSPLASIA AND GASTRIC CANCER PATIENTS

Serum levers of retinol, α-tocopherol, β-carotene and elements(Zn, Cu, Mn, Ca, Mg, Cr, Co, Cd, Mo, Se)were detemined in 45 gastric cancer and 41 gastric dysplasia patients, and 48 normal subjects. The results showed that βcarotene and Se, Co were lower in gastric cancer patients than that in gastric dysplasia patients or in normal subjects ,Ni and Cr levels were lower and Mn , Ca and Cd were higherin gastric cancer than in dysplasia patients. Zn , Fe , Cr . Cdwere lower and Mn, Ca, Mg. Mo levels were higher in gastric cancer patients than in normal. The differences mentioned are statistically significant. The stepwise discriminant analysis of 10 variables( Mn, Fe, Ca, Cr,Mo, Co, Cd, Se, α-tocophrol, β-carotene) were used in identifying gastric cancer . with 100% of the positive rate.The potential protective effect of β-carotene and Se against gastric cancer is an interesting postulate. We suggest that optimum supplement of β- carotene and Se might will be beneficial to gastric dysplasia patients in preventing the development of gastric cancer.

A white opaque substance-positive gastric hyperplastic polyp with dysplasia

The endoscopic findings of gastric hyperplastic polyps (HPs) with dysplasia have not been well-defined, and the clinical significance of these lesions, including their malignant potential, is unclear. In this report, we describe a case of a white opaque substance (WOS)positive gastric HP with dysplasia. A 76-year-old woman was referred to our hospital for endoscopic resection of a gastric HP. Upper endoscopy revealed a 25-mm whitish and reddish polypoid lesion on the greater curvature in the lower third of the stomach. The whitish part was diagnosed as a WOS using conventional and magnifying endoscopy with narrow band imaging. An examination of the biopsy specimen indicated that the lesion was a typical gastric HP. However, because of its color and the presence of a WOS, we suspected that this lesion was an atypical gastric HP. Therefore, we performed a polypectomy. Histopathologically, diffuse lowto high-grade dysplasia was found on the surface of the polyp. We performed immunohistochemical staining using a monoclonal antibody specific for adipophilin as a marker of lipid droplets (LDs). LDs were detected in approximately all of the neoplastic cells, especially in the surface epithelium of the intervening apical parts and were located in the subnuclear cytoplasm of the neoplastic cells. According to endoscopic and histopathological findings, the WOS-positive epithelium indicated dysplasia of the gastrointestinal phenotype, which could absorb lipids. The presence of a WOS in a gastric HP may be considered an endoscopic finding that is predictive of the neoplastic transformation of a gastric HP. We suggest that a WOS-positive gastric HP should be resected endoscopically to investigate its neoplastic transformation.

A NEWLY RECOGNIZED PRECANCEROUS LESION OF THE STOMACH (HISTOPATHOLOGIC FEATURES OF GLOBOID DYSPLASIA OF HUMAN GASTRIC EPITHELIUM)

The histopathological features of the globoid dysplasia of the human gastric epithelium were described in detail and in series by means of observation of serial sections of 61 cases with globoid dys-plasias. Three grades were divided according to the architectural and cellular atypia of the globoid dys-plasias. The penetration of outer layer globoid dys-plastic cells through the basement membrane of 'the structure of double layers' appeared in typical globoid dysplasia grade II and the infiltration of the globoid dysplastic cells into stroma as well as the formation of incipient focus of signet ring cell carcinoma were described. The twinkling scene of the infiltration of the globoid dysplastic cells into lamina propria through the basement membrane, and the destroying of the basement membrane by the globoid dysplastic cells were shown by means of Gordon Sweet's staining. Through the analysis as for the distribution characteristics of ages and sexes in 61 globoid dysplasia cases and 51 signet ring cell carcinomas, a fact was discovered that the mobility of female cases was ten years prior to that of male ones in average. A conclusion could be made that the globoid dysplasia might be an important precan-cerous lesion of the signet ring cell carcinoma of the stomach.

Gastric xanthelasma and metabolic disorders: A large retrospective study among Chinese population

AIM To gain knowledge of xanthelasma,a large populationbased study was conducted. METHODS Patients who underwent upper gastrointestinal endoscopy at the First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou,China during Jan 2009 to Nov 2016 were included. General characteristics as well as clinical data were collected,including blood routine,serum biochemical analysis,endoscopic findinds,histological evaluation and comorbiditie. Statistical analyses was performed using SPSS 20.0 software for Windows(IBM Inc.,Chicago,IL,United States) using Student's t-test,Mann-Whitney U test,χ2 test,univariable and multivariable logistic analysis. 2-tailed P value less than 0.05 was considered to be statistically significant. RESULTS A total of 176006 endoscopies were retrieved and we included 1370 xanthelasma participants(703 men,667 women) in this study. Prevalence of xanthelasma was 0.78% with average age of 56.6 ± 11.2 years. Chief complaint of xanthelasma consisted abdominal pain (24.2%),up-abdominal discomfort(14.1%),abdominal distention(10.1%),dyspepsia(9.1%),et al. Most xanthelasma occurred as single lesion in gastric antrum. Xanthelasma patients witnessed higher Helicobacter pylori(H. pylori) infection rate,more of other gastric lesions including atrophy,intestinal metaplasia and dysplasia(P < 0.01). In xanthelasma patients,serum carcinoembryonic antigen,triglyceride,fasting glucose,neutrophil,neutrophil-to-lymphocyte ratio were significantly higher,and high density lipoprotein-cholesterol,lymphocyte was lower(P < 0.05). Xanthelasma accompanied with more fatty liver disease and hepatic cyst,but fewer gallbladder polyp(P < 0.05). In logistic regression,it revealed that fasting plasma glucose(OR = 3.347,1.170-9.575,P < 0.05),neutrophil(OR = 1.617,1.003-2.605,P < 0.05),and carcinoembryonic antigen(OR = 2.011,1.236-3.271,P < 0.01) were all independent risk factors in xanthelasma. CONCLUSION Current study described a large xanthelasma cohort in Chinese population,revealed its relationship with H. pylori infection,carcinogenesis,metabolic dysfunction and inflammation as well.

Microsatellite instability in gastric cancer and pre-cancerous lesions

AIM: To investigate the microsatellite instability (MSI) in cancer and pre-cancerous lesions of the stomach and its mechanisms underlying the development of gastric cancer.METHODS: Thirty-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.RESULTS: The 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.CONCLUSION: Accumulation 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.

Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis

Fundic gland polyps are now commonly recognized during endoscopy. These polyps are benign, often multiple and usually detected in the gastric body and fundus. In the past, these polyps were sometimes associated with familial adenomatous polyposis. In recent years, it has become evident that increasing numbers of these polyps are being detected during endoscopic studies, particularly in patients treated with proton pump inhibitors for prolonged periods. In some, dysplastic changes in these polyps have also been reported. Recent studies have suggested that there may be no increase in risk of colon cancer with long-term proton pump inhibitor therapy. While temporarily reassuring, ongoing vigilance, particularly in those genetically predisposed to colon cancer, is still warranted.

Screening for and surveillance of gastric cancer

Although the prevalence of gastric cancer(GC) progressively decreased during the last decades,due to improved dietary habit,introduction of food refrigeration and recovered socio-economic level,it still accounts for 10% of the total cancer-related deaths. The best strategy to reduce the mortality for GC is to schedule appropriate screening and surveillance programs,that rises many relevant concerns taking into account its worldwide variability,natural history,diagnostic tools,therapeutic strategies,and cost-effectiveness. Intestinal-type,the most frequent GC histotype,develops through a multistep process triggered by Helicobacter pylori(H. pylori) and progressing from gastritis to atrophy,intestinal metaplasia(IM),and dysplasia. However,the majority of patients infected with H. pylori and carrying premalignant lesions do not develop GC. Therefore,it remains unclear who should be screened,when the screening should be started and how the screening should be performed. It seems reasonable that screening programs should target the general population in eastern countries,at high prevalence of GC and the high-risk subjects in western countries,at low prevalence of GC.As far as concern surveillance,currently,we are lacking of standardized international recommendations and many features have to be defined regarding the optimal diagnostic approach,the patients at higher risk,the best timing and the cost-effectiveness.Anyway,patients with corpus atrophic gastritis,extensive incomplete IM and dysplasia should enter a surveillance program.At present,screening and surveillance programs need further studies to draw worldwide reliable recommendations and evaluate the impact on mortality for GC.

Role of submucosal injection in radiofrequency ablation of gastric low-grade dysplasia:Effects on symptoms and outcomes

Background:To date,there is still a lack of standardized management strategies for gastric low-grade dysplasia(LGD),which is a direct neoplastic precancerous lesion and requires specifically superficial destruction.Radiofrequency ablation(RFA)is expected to be an effective method for gastric LGD,but post-RFA pain may affect patients’satisfaction and compliance.The current study aimed to evaluate the value of a submucosal injection prior to RFA(SI-RFA)for postoperative pain and treatment outcomes.Methods:Between October 2014 and July 2021,gastric LGDs without risk factors(size>2 cm,unclear boundary,and abnormal microsurface and microvascularity)undergoing regular RFA and SI-RFA were retrospectively analyzed.Postoperative pain scores,wound healing,and clinical efficacy were compared.Propensity score matching,stratified analysis,and multivariable logistic regression were performed to control the confounding variables.Results:One hundred and ninety-seven gastric LGDs in 151 patients received regular RFA.Forty-nine gastric LGDs in 36 patients received SI-RFA.Thirty-six pairs of patients were selected for the assessment of postoperative pain by propensity score matching.Compared to regular RFA,SI-RFA significantly decreased the degree and duration of postoperative pain(OR,0.32;95%CI,0.13-0.84;P=0.020),improved wound healing rate(80.0%[36/45]vs.58.9%[89/151],P=0.012),increased the complete ablation rate(91.8%[45/49]vs.86.3%[170/197],χ^(2)=1.094,P=0.295),but correlated with higher rates of local recurrence and progression(25.6%[10/39]vs.13.2%[18/136],χ^(2)=3.471,P=0.062;8.3%[3/36]vs.0.9%[1/116],P=0.042).The multivariable logistic regression model confirmed that submucosal injection was associated with local recurrence(OR,2.93;95%CI,1.13-7.58;P=0.027).Conclusions:Submucosal injections prior to RFA may reduce postoperative pain and scar formation while ensuring complete ablation of gastric LGD.However,local recurrence and progression should be considered seriously.

Identifying high-risk individuals for gastric cancer surveillance from western and eastern perspectives: Lessons to learn and possibility to develop an integrated approach for daily practice

Current evidence shows that individuals with gastric dysplasia, severe and extensive gastric atrophy, extensive gastric intestinal metaplasia and the incomplete subtype of intestinal metaplasia are at high risk for gastric cancer(GC) development. There are several approaches to identifying these subjects,including noninvasive methods, esophagogastroduodenoscopy and histology.The main approach in Western countries is histology-based while that in Eastern countries with a high prevalence of GC is endoscopy-based. Regarding asymptomatic individuals, the key issues in selecting applicable approaches are the ability to reduce GC mortality and the cost-effectiveness of the approach. At present, population-based screening programs have only been applied in a few Asian countries with a high risk of GC. Pre-endoscopic risk assessment based on demographic and clinical features, such as ethnicity, age, gender, smoking and Helicobacter pylori status, is helpful for identifying subjects with high pre-test probability for a possibly cost-effective approach, especially in intermediate-and low-risk countries. Regarding symptomatic patients with indications for esophagogastroduodenoscopy, the importance of opportunistic screening should be emphasized. The combination of endoscopic and histological approaches should always be considered as endoscopy provides a real-time assessment of the patient’s risk level. In addition, imaging enhanced endoscopy(IEE) has been shown to facilitate targeted biopsies resulting in better correlation between endoscopic and histological findings. Currently, the use of IEE is recommended for endoscopic examinations, and the Operative Link for Gastric Intestinal Metaplasia or Operative Link on Gastritis Assessment grading systems are recommended for histological examinations whenever available. However,resource limitations are an important barrier in many regions worldwide. Thus,for an approach to be applicable in real-life practice, it should be not only evidence-based but also resource-sensitive. In this review, we discuss the current understanding and approaches to identifying high-risk individuals from western and eastern perspectives, as well as the possibility of an integrated, resourcesensitive approach.

Possible involvement of leptin and leptin receptor in developing gastric adenocarcinoma

AIM： To investigate the expression of leptin and leptin receptor （ob-R） in intestinal-type gastric cancer and precancerous lesions, and to explore the possible mechanism and role of the leptin system in developing intestinal-type gastric adenocarcinoma.METHODS： Immunohistochemistry was performed to examine the expression of leptin and leptin receptor in archival samples of gastric adenocarcinoma and preneoplastic lesions, including intestinal metaplasia and mild to severe gastric epithelial dysplasia. Positive staining was identified and percentage of positive staining was graded.RESULTS： Dual expression of leptin and leptin receptor were detected in 80% （16/20） intestinal metaplasia, 86.3% （25/30） mild gastric epithelial dysplasia, 86.7% （26/30） moderate gastric epithelial dysplasia, 93.3% （28/30） severe gastric epithelial dysplasia, 91.3% （55/60） intestinal-type gastric adenocarcinoma and 30.0% （9/30） diffuse-type gastric carcinoma. The percentage of dual expression of leptin and leptin receptor in intestinal-type gastric adenocarcinoma was significantly higher than that in diffuse-type gastric adenocarcinoma （χ^2 = 37.022, P〈0.01）.CONCLUSION： Our results indicate the presence of an autocrine loop of leptin system in the development of intestinal-type gastric adenocarcinoma.

Aberrant Eph B/ephrin-B expression in experimental gastric lesions and tumor cells

AIM: To determine whether the expression profiles of Eph B receptor and ephrin-B ligand can be used as markers for dysplastic/oncogenic transformation in gastric mucosa.METHODS: The protein expression and localization ofEph B and ephrin-B in normal, ulcerated regenerating, and dysplastic gastric mucosa were examined in a rat experimental model by immunolabeling, and m RNA expression was assessed in four human gastric carcinoma cell lines by reverse transcription-polymerase chain reaction.RESULTS: Ephrin-B- and Eph B-expressing regions were divided along the pit-gland axis in normal gastric units. Eph B2 was transiently upregulated in the experimental ulcer, and its expression domain extended to gastric pits and/or the luminal surface where ephrin-B-expressing pit cells reside. Eph B2, B3, and B4 and ephrin-B1 were coexpressed in the experimental gastric dysplasia, and more than one ligand-receptor pair was highly expressed in each of the gastric carcinoma cell lines.CONCLUSION: Robust and stable coexpression of Eph B and ephrin-B is a feature common to experimentally induced gastric dysplasia and human gastric carcinoma cell lines as compared to normal gastric and ulcerated regenerating epithelia. Thus, Eph B/ephrin-B may be a useful marker combination for dysplastic/oncogenic transformation in gastric cancer.

Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas

AIM:To understand the implication of GATA-4 and GATA-5 methylation in gastric carcinogenesis.METHODS: Methylation status of GATA-4 and GATA-5 CpG islands in human gastric mucosa samples, including normal gastric biopsies from 45 outpatients, gastric dysplasia [low-grade gastric intraepithelial neoplasia (GIN), n = 30; indefinite, n = 77], and 80 paired spo- radic gastric carcinomas (SGC) as well as the adjacent non-neoplastic gastric tissues was analyzed by methylation specific polymerase chain reaction (MSP) and confirmed by denatured high performance liquid chromatography (DHPLC). Immunohistochemical staining was used to detect protein expression. The correlation between GATA-4 and GATA-5 methylation and clinicopathological characteristics of patients including Helicobacter pylori (H. pylori) infection was analyzed.RESULTS:GATA-4 and GATA-5 methylation was frequently observed in SGCs (53.8% and 61.3%, respectively) and their corresponding normal tissues (41.3% and 46.3%) by MSP. The result of MSP was consistent with that of DHPLC. Loss of both GATA-4 and GATA-5 proteins was associated with their methylation in SGCs (P = 0.01). Moreover, a high frequency of GATA-4 and GATA-5 methylation was found in both gastric low-grade GIN (57.1% and 69.0%) and indefinite for dysplasia (42.9% and 46.7%), respectively. However, GATA-4 and GATA-5 methylation was detected only in 4/32 (12.5%) and 3/39 (7.7%) of normal gastric biopsies. GATA-4 methylation in both normal gastric mucosa and low-grade GIN was also significantly associated with H. pylori infection (P=0.023 and 0.027, two-sides).CONCLUSION: Epigenetic inactivation of GATA-4 (and GATA-5) by methylation of CpG islands is an early freuent event during gastric carcinogenesis and is significantly correlated with H. pylori infection.

Aberrant DNA-PKcs and ERGIC1 expression may be involved in initiation of gastric cancer

AIM to investigate the molecular mechanisms of gastric carcinogenesis.METHODS We used label-free quantification technology integrated with liquid chromatography-tandem mass spectrometry(Lc-m S/m S) analysis to identify differentially expressed proteins in 160 specimens of normal gastric mucosa,gastric mucosa with mild dysplasia,moderate dysplasia,severe dysplasia,and early mucosal gastric cancer(Gc) collected at the Second Hospital of Lanzhou University from 2010 to 2015. Immunohistochemistry was used to verify the differentially expressed proteins detected by Lc-m S/m S.RESULTS With a threshold of a 1.2-fold change and a P-value< 0.05 between mild dysplasia,moderate dysplasia,severe dysplasia or early mucosal Gc and matched normal gastric mucosa tissues,proteomic analysis identified 365 significantly differentially expressed proteins. Er GIc1 expression decreased,while DNAPKcs expression increased gradually along with different stages of Gc initiation based on the tendency of fold change. the expression patterns of Er GIc1 and DNA-PKcs revealed by immunohistochemistry were consistent with the Lc-m S/m S results.CONCLUSION the results suggest that aberrant Er GIc1 and DNAPKcs expression may be involved in Gc initiation.

Peculiarity of Precursors of Gastric Cancer and its Relationship with Diets in Northern China Inhabitants

Types and characteristics of gastric dysplasia werestudied histopathologically. Besides the adenomatous,cryptal and globoid dysplasias, regenerative type of gas-tric dysplasia was described, especially about its histo-pathological features and histogenesis. The peculiarityof this type of gastric dysplasia just coincided with thefindings of gastric mucosal changes found in the inhabitantsliving in Liaodong Panisula-a high incidence area ofgastric cancer. According to the epidemiologic and histo-pathologic studies on the inhabitants of Zhuanghe Countyof Liaodong Panisula, it was found that high salted foodse.g. the salted pork and fish etc. showed strongmutagenecity. The authors detected that these were therisk factors and might be the leading cause of the gastricmucosal erosions and following by epithelial regenerativechanges. Malignant changes were detected in the regene-rative dysplastic lesions in pathologic sections. Therefore,gastric mucosal regeneration should not be oper looked asa precursor of gastric cancer in some cases.

Treatment strategy for gastric non-invasive intraepithelial neoplasia diagnosed by endoscopic biopsy

Treatment strategies,whether as follow-up or"total incisional biopsy"for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen,are controversial due to problems associated with the diagnostic accuracy of endoscopic forceps biopsy and questions about the safety and efficacy of endoscopic treatment.Based on the histological findings of the biopsy specimen,it is difficult to differentiate between reactive or regenerative changes,inflammation and neoplastic changes,intraepithelial and invasive tumors.Therefore,gastric neoplasia diagnosed as noninvasive intraepithelial often develop into invasive carcinoma during follow-up.Recent advances in endoscopic modalities and treatment devices,such as image-enhanced endoscopy and highfrequency generators,may make endoscopic treatment,such as endoscopic submucosal dissection(ESD),a therapeutic option for gastric intraepithelial neoplasia,including low-grade neoplasms.Future studies are required to evaluate whether ESD is a valid strategy for gastric intraepithelial neoplasm with regard to safety and cost effectiveness.

Carcinogenic Helicobacter pylori in gastric pre-cancer and cancer lesions: Association with tobacco-chewing

AIM: To investigate the low gastric cancer incidence rate relative to the highly prevalent Helicobacter pylori (H. pylori) infection; data relevant to H. pylori infection during gastric carcinogenesis in Indian patients is currently lacking.

Premalignant lesions and gastric cancer: Current understanding

Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In this review we reflect upon the historic approaches to describing premalignant lesions and GC,highlight the current molecular landscape and how this could inform future risk assessment prevention strategies.