Clinical pathological characteristics of“crawling-type”gastric adenocarcinoma cancer:A case report

BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC that has unique histopathological and clinical characteristics,and its diagnosis and management can be challenging.This pathological type of GC is also rare.CASE SUMMARY Here,we report the case of a patient who underwent ordinary endoscopy,na-rrow-band imaging,and endoscopic ultrasonography intending to determine the extent of tumor invasion and upper abdominal enhanced computed tomography and whether there was tumor metastasis.Then,endoscopic submucosal dissection was performed.After pathological and immunohistochemical examination,the pathological diagnosis was crawling-type gastric adenocarcinoma.This is a very rare and special pathological type of tumor.This case highlights the importance of using advanced endoscopic techniques and pathological examination in diagnosing and managing gastric crawling-type adenocarcinoma.Moreover,the findings underscore the need for continued research and clinical experience in this rare subtype of GC to improve patient outcomes.CONCLUSION The“crawling-type”GC is a rare and specific tumor pathology.It is difficult to identify and diagnose gliomas via endoscopy.The tumor is ill-defined,with a flat appearance and indistinct borders due to the lack of contrast against the background mucosa.Pathology revealed that the tumor cells were hand-like,so the patient has diagnosed with“crawling-type”gastric adenocarcinoma.

Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed statistically significant better OS than the low PNI groups.In multivariate analyses,low PNI was repeatedly recognised as an independent prognostic factor for poor survival.CONCLUSION According to the present study,low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.

Role of savolitinib in advanced gastric adenocarcinoma with meningeal carcinomatosis and cerebellar metastasis:A case report

BACKGROUND Brain metastases(BM)are very rare in gastric adenocarcinoma(GaC),and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness.However,its pathogenesis remains unclear.Genetic testing revealed cellular-mesenchymal epithelial transition factor receptor(MET)amplification.Therefore,treatment with savolitinib,a small molecule inhibitor of c-Met,was selected.CASE SUMMARY A 66-year-old woman was diagnosed with advanced GaC 6 months prior to presentation due to back pain.Cerebellar and meningeal metastases were observed during candonilimab combined with oxaliplatin and capecitabine therapy.The patient experienced frequent generalized seizures and persistent drowsiness in the emergency department.Genetic testing of cerebrospinal fluid and peripheral blood revealed increased MET amplification.After discussing treatment options with the patient,savolitinib tablets were administered.After a month of treatment,the intracranial lesions shrank considerably.CONCLUSION BM is very rare in advanced GaC,especially in meningeal cancer,that is characterized by rapid disease deterioration.There are very few effective treatment options available;however,technological breakthroughs in genomics have provided a basis for personalized treatment.Furthermore,MET amplification may be a key driver of BM in gastric cancer;however,this conclusion requires further investigation.

Prognostic value of claudin 18.2 expression in gastric adenocarcinoma

BACKGROUND Claudin 18.2(CLDN18.2)is a cell surface protein expressed by gastric cancer cells.The monoclonal antibody zolbetuximab binds CLDN18.2-positive cancer cells and causes cancer cell death.A few studies researched the prognostic effect of CLDN18.2 expression in metastatic gastric adenocarcinoma.AIM To identify the prognostic value of CLDN18.2 expression in patients with metastatic gastric adenocarcinoma.METHODS This study was conducted with 65 patients over the age of 18 who were diagnosed with metastatic gastric adenocarcinoma.We investigated the effect of CLDN18.2 expression on clinicopathological characteristics(age,sex,histological grade,Lauren classification,family history,metastatic site,HER2 expression)and prognosis for patients with metastatic gastric adenocarcinoma.RESULTS CLDN18.2 expression was positive in 73.8%(48)of the patients.During the median 17.7-mo follow-up period,89.2%(58)of the patients died.Median progression-free survival and overall survival(OS)were 6 mo(95%confidence interval:1.6-10.4)and 12 mo(95%confidence interval:7.5-16.5).There was no statistically significant correlation between CLDN18.2 expression and clinicopathological characteristics of the patients.In univariate and multivariate Cox regression analysis,there was no correlation between clinicopathological characteristics of patients and progression-free survival or OS.CONCLUSION CLDN18.2 expression was quite high in patients with gastric adenocarcinoma,identifying the proportion of the patients in whom zolbetuximab would be efficacious.There is no statistically significant correlation with clinicopathological characteristics and OS.CLDN18.2 is not a prognostic marker in patients with gastric adenocarcinoma,although it is predictive.

Comparing effectiveness and safety of paclitaxel plus raltitrexed vs. paclitaxel alone in second-line palliative chemotherapy for metastatic gastric adenocarcinoma: A randomized phase Ⅱ clinical trial

Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric cancer.This study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment in metastatic gastric cancer(MGC)patients.Methods:An open,randomized,multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP[raltitrexed(3 mg/m^(2)on day 1)and paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]or P[paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]as 2nd-line chemotherapy.The primary endpoint was progression-free survival(PFS).The secondary endpoints were the overall response rate(ORR),overall survival(OS),and safety.Results:PFS had a tendency to be prolonged with RP compared to P(2.7 months vs.1.7 months;P=0.148).OS was also prolonged with RP compared to P(10.2 months vs.6.1 months;P=0.140).The ORR was equal in the RP and P groups(6.8%and 4.0%;P=0.72).The disease control rate(DCR)in the RP and P groups was 56.2%and 36.0%,respectively.Grade 3-4 treatment-related adverse events occurred in 36.2%(RP)and 28.2%(P)of patients.Frequent grade 3-4 toxicities for RP and P were neutropenia(11.0%and 4.0%),anemia(1.4%and 4.0%),and thrombocytopenia(1.4%and 5.3%),and all grades of peripheral neurotoxicity(12.3%vs.17.3%).All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4%and 14.1%).Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement,the OS of the RP regimen was longer(P=0.05).Conclusions:Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS,especially among patients with ascites or peritoneal involvement,which warrants confirmation using larger sample studies.

Role of pre-existing incomplete intestinal metaplasia in gastric adenocarcinoma:A retrospective case series analysis

BACKGROUND Risk stratification for patients with gastric precancerous lesions for endoscopic surveillance remains controversial.AIM To analysis of patients having developed gastric adenocarcinoma during the period of follow-up.METHODS We conducted a retrospective study on patients having undergone upper endoscopy prior to the development of gastric adenocarcinoma. The presence and stage of precancerous lesions as well as subtype of intestinal metaplasia at the baseline endoscopy got evaluated. Literature mini-review was performed.RESULTS Out of 1681 subjects in the Biobank, gastric adenocarcinoma was detected in five cases in whom previous endoscopy data with biopsies either from the corpus or antral part were available. All of the patients had incomplete intestinal metaplasia during the baseline endoscopy;all three subjects in whom intestinal metaplasia subtyping was performed according to Filipe et al, had Type Ⅲ intestinal metaplasia. Two of the five cases had low Operative Link on Gastritis Assessment(OLGA) and Operative Link on Gastritis Intestinal Metaplasia Assessment(OLGIM) stages(Ⅰ-Ⅱ) at the baseline.CONCLUSION The presence of incomplete intestinal metaplasia, in particular, that of Type Ⅲ is a better predictor for gastric adenocarcinoma development than OLGA/OLGIM staging system. Subtyping of intestinal metaplasia have an important role in the risk stratification for surveillance decisions.

Effects of JAG-1 on the Proliferation and Migration of Gastric Adenocarcinoma Cells after TRAIP Knockout

[Objectives]To study the effects of JAG-1 on silencing TRAIP(tumor necrosis factor receptor associated factor interaction protein)after regulating Notch signaling pathway on the proliferation and migration of gastric adenocarcinoma cells.[Methods]Gastric adenocarcinoma cells were categorized into si-NC+DMSO(control+DMSO),si-TRAIP#1+DMSO(transfected with TRAIP+DMSO),si-NC+JAG-1(control+JAG-1),and si-TRAIP#1+JAG-1(transfected with TRAIP+JAG-1),and the proliferation of the cells was detected by CCK-8 assay and plate colony formation assay.Transwell assay was used to detect cell migration,and Western blot was adopted to detect the expression of proliferation-associated protein CyclinD1,migration-associated protein MMP2,and key proteins of Notch signaling pathway Notch1,Hes1 and Jagged1.[Results]Compared with siTRAIP#1+DMSO,the gastric adenocarcinoma cells in si-TRAIP#1+JAG-1 group showed increased proliferation and migration(P<0.05),and there was a significant increase in the expression of CyclinD1,MMP2,Notch1,Hes1,and Jagged1(P<0.05).[Conclusions]After TRAIP knockdown,JAG-1 increased not only the proliferation and migration ability of gastric adenocarcinoma cells,but also the expression of key proteins of Notch signaling pathway Notch1,Hes1,and Jagged1.

Gastric adenocarcinoma of the fundic gland(chief cell-predominant type): A review of endoscopic and clinicopathological features

Gastric adenocarcinoma of the fundic gland(chief cellpredominant type, GA-FG-CCP) is a rare variant of welldifferentiated adenocarcinoma, and has been proposed to be a novel disease entity. GA-FG-CCP originates from the gastric mucosa of the fundic gland region without chronic gastritis or intestinal metaplasia. The majority of GA-FG-CCPs exhibit either a submucosal tumor-like superficial elevated shape or a flat shape on macroscopic examination. Narrow-band imaging with endoscopic magnification may reveal a regular or an irregular microvascular pattern, depending on the degree of tumor exposure to the mucosal surface. Pathological analysis of GA-FG-CCPs is characterized by a high frequency of submucosal invasion, rare occurrences of lymphatic and venous invasion, and low-grade malignancy. Detection of diffuse positivity for pepsinogen-I by immunohistochemistry is specific for GA-FG-CCP. Careful endoscopic examination and detailed pathological evaluation are essential for early and accurate diagnosis of GA-FG-CCP. Nearly all GA-FG-CCPs are treated by endoscopic resection due to their small tumor size and low risk of recurrence or metastasis.

Gastric adenocarcinoma of fundic gland type with signet-ring cell carcinoma component: A case report and review of the literature

A depressed lesion was found at a gastric angle of 76-yearold Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection(ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-Ⅰ, diffusely MUC6, and scattered H^+/K^+ ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type(GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, i.e., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.

Gastric adenocarcinoma of fundic gland type: Five cases treated with endoscopic resection

Recently,a new disease entity termed gastric adenocarcinoma of fundic gland type(GA-FG) was proposed.We treated five cases of GA-FG with endoscopic submucosal dissection.All tumors were small and located in the upper third of the stomach.Four tumors were macroscopically identified as 0-IIa and one was identified as 0-Ⅱb.Narrow-band imaging with magnifying endoscopy showed an irregular microvascular pattern in 2 cases and a regular microvascular pattern in the remainder.All tumors arose from the deep layer of the lamina propria mucosae and showed submucosal invasion.Lymphatic invasion was seen only in one case,while no venous invasion was recognized.All tumors were positive for pepsinogen-Ⅰ and MUC6 by immunohistochemistry.None showed p53 overexpression,and the labeling index of Ki-67 was low in all cases.All cases have been free from recurrence or metastasis.Herein,we discussed the clinicopathological features of GA-FG in comparison with past reports.

Multiple gastric adenocarcinoma of fundic gland type: A case report

BACKGROUND In recent years, there have been reports of a new histological type of gastric cancer, termed gastric adenocarcinoma of the fundic gland (GA-FG). This disease entity presents differentiation towards the fundic gland, especially chief cellpredominant differentiation (GA-FG-CCP). GA-FG-CCP easily invades into the submucosa but rarely shows metastasis. The reports mostly describe primarily single lesions. Herein, we report a case with multiple lesions, and summarize the clinicopathologic characteristics of multiple cases. CASE SUMMARY A 55-year-old woman underwent upper gastrointestinal endoscopy screening. Two whitish lesions on the anterior wall of the gastric corpus and the gastric fundus were detected. The patient had previously received Helicobacter pylori eradication therapy. The mucosa was characterized as grade C-2 atrophic gastritis. We diagnosed the patient with multiple GA-FG (GA-FG-CCP) by hematoxylin and eosin (HE) staining and immunohistochemical staining of the endoscopic biopsy. Upon performing endoscopic submucosal dissection (ESD), one lesion was not found, but the scar from the biopsy was visible;the mucularis mucosa of the biopsy and ESD-resected specimen were intact. The two lesions showed no lymphatic nor venous invasion. The resection performed appeared to be relatively curative. CONCLUSION Cases of multiple GA-FG-CCP are very rare in clinical practice. Most of its clinicopathologic characteristics are similar to those of a single lesion. Our case provides diagnostic and therapeutic information about GA-FG-CCP with multiple lesions.

Combination chemotherapy with paclitaxel,cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma:a multicenter prospective study

Objective： To evaluate the efficacy and toxicity of the combination regimen of paclitaxel, cisplatin and 5-FU （PCF） as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction （EGJ） adenocarcinoma in China. Methods： The patients were treated with paclitaxel 150 mg/m2 on dl; fractionated cisplatin 15 mg/m2 and continuous infusion 5-FU 600 mg/（mLd） intravenously on d 1-d5 of a 21-d cycle until disease progression or unacceptable toxicities. Results： Seventy-five patients have been enrolled, among which, 41 received PCF regimen as the first-line therapy （group A） and 34 received the regimen as the second-line therapy （group B） with the median age of 59 years old and Karnofsky performance status （KPS） score 〉80. Toxicities were analyzed in all 75 patients. Seventy-one patients were evaluable for efficacy. The median overall survival （mOS） was 12.0 months （95% CI： 7.9-16.2 months） in group A and 7.3 months （95% CI： 4.3-10.3 months） in group B, respectively. The median progression-free survival （mPFS） was 5.7 months （95% CI： 4.1-7.2 months） and 5.0 months （95% CI： 3.1-6.9 months）, respectively. The response rate （CR^PR） was 40% （16/40; 95% CI： 24.9-56.7%） in group A and 22.6% （7/31; 95% CI： 9.6-41.1%） in group B. Major grade 3 or 4 adverse events include neutropenia （41.3 %）, febrile neutropenia （9.3 %）, nausea/anorexia （10.7%）, and vomiting （5.3 %）. There was no treatment-related death. Conclusions： The combination chemotherapy with PCF is active and tolerable as first-line and second- line therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma. The response and survival of PCF are same as those of DCF, but the tolerance is much better.

Differential gene expression profiling of gastric intraepithelial neoplasia and early-stage adenocarcinoma

AIM:To investigate the differentiated whole genome expression profiling of gastric high-and low-grade intraepithelial neoplasia and early-stage adenocarcinoma.METHODS:Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013.Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia(LGIN),20 high-grade intraepithelial neoplasia(HGIN),19 early-stage adenocarcinoma(EGC),and 19 chronic gastritis tissue samples using Agilent 4×44K Whole Human Genome microarrays.Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm.A gene ontology(GO)enrichment analysis was performed using the Gene Spring software GX 12.6.The differentially expressed gene was verified using a real-time TaqManPCR assay with independent tissue samples,including 26 LGIN,15 HGIN,14 EGC,and 20 chronic gastritis.The expression of G0S2 were further validated by immunohistochemical staining(IHC)in 24 LGIN,40 HGIN,30 EGC and 61 chronic gastritis specimens.RESULTS:The gene expression patterns of LGIN and HGIN tissues were distinct.There were 2521 significantly differentially expressed transcripts in HGIN,with951 upregulated and 1570 downregulated.A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism,defense response,and nuclear factorκB(NF-κB)cascade.While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues,only 38 transcripts were upregulated in EGC.A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC.It is worth noting that,compared with LGIN,289 transcriptswere expressed at higher levels both in HGIN and EGC.A characteristic gene,G0/G1 switch 2(G0S2)was one of the 289 transcripts and related to metabolism,the immune response,and the NF-κB cascade,and its expression was validated in independent samples through real-time TaqManPCR and immunohistochemical staining.In real-time PCR analysis,the expression of G0S2 was elevated both in HGIN and EGC compared with that in LGIN(P<0.01 and P<0.001,respectively).In IHC analysis,G0S2 immunoreactivity was detected in the cytoplasmic of neoplastic cells,but was undetectable in chronic gastritis cells.The G0S2 expression in HGIN was higher than that of LGIN(P=0.012,χ2=6.28)and EGC(P=0.008,χ2=6.94).CONCLUSION:A clear biological distinction between gastric high-and low-grade intraepithelial neoplasia was identified,and provides molecular evidence for clinical application.

Gastric metastasis from primary lung adenocarcinoma mimicking primary gastric cancer

Gastric metastases from lung adenocarcinoma are rare. Because gastric metastasis grossly resembles advanced gastric cancer, it is difficult to diagnose gastric metastasis especially when the histology of the primary lung cancer is adenocarcinoma. We describe a case of gastric metastasis from primary lung adenocarcinoma mimicking Borrmann type Ⅳ primary gastric cancer. A 68-year-old man with known lung adenocarcinoma with multiple bone metastases had been experiencing progressive epigastric pain and dyspepsia over one year. Esophagogastroduodenoscopy revealed linitis plasticalike lesions in the fundus of the stomach. Pathologic examination revealed a moderately differentiated adenocarcinoma with submucosal infiltration. Positive immunohistochemical staining for thyroid transcription factor-1(TTF-1) and napsin A(Nap-A) confirmed that the metastasis was pulmonary in origin. The patient had been treated with palliative chemotherapy for the lung cancer and had lived for over fifteen months after the diagnosis of gastric metastasis. Clinicians should be aware of the possibility of gastric metastasis in patients with primary lung adenocarcinoma, and additional immunohistochemical staining for Nap-A as well as TTF-1 may help in differentiating its origin.

Clonality analysis of neuroendocrine cells in gastric adenocarcinoma

AIM:To achieve a better understanding of the origination of neuroendocrine(NE)cells in gastric adenocarcinoma.METHODS:In this study,120 cases of gastric adenocarcinoma were obtained.First,frozen section-immunohistochemistrical samples were selected from a large quantity of neuroendocrine cells.Second,laser capture microdissection was used to get target cells from gastric adenocarcinoma and whole genome amplification was applied to get a large quantity of DNA for further study.Third,genome-wide microsatellite abnormalities[microsatellite instability(MSI),loss of heterozygosity (LOH)]and p53 mutation were detected by polymerase chain reaction(PCR)-single-strand conformation polymer-phism-silver staining and PCR-sequencing in order to identify the clonality of NE cells.RESULTS:The total incidence rate of MSI was 27.4%,while LOH was 17.9%.Ten cases had a highest concordance for the two types of cells.The other samples had similar microsatellite changes,except for cases 7 and10.Concordant p53 mutations exhibited in sample 4,14,21 and 27,and there were different mutations between two kinds of cells in case 7.In case 17,mutation took place only in adenocarcinoma cells.p53 mutation was closely related with degree of differentiation,tumor-node-metastasis stage,vessel invasion and lymph node metastasis.In brief,NE and adenocarcinoma cells showed the same MSI,LOH or p53 mutation in most cases(27/30).In the other three cases,different MSI,LOH or p53 mutation occurred.CONCLUSION:NE and the gastric adenocarcinoma cells may mainly derive from the same stem cells,but the remaining cases showing different origin needs further investigation.

Association of genotypes of rs671 within ALDH2 with risk for gastric cardia adenocarcinoma in the Chinese Han population in high-and low-incidence areas

Objective: This study aimed to determine if gastric cardia adenocarcinoma(GCA) risk was associated with the lys(A or *2) allele at the rs671(glu504lys) polymorphism within the aldehyde dehydrogenase 2(ALDH2) gene in a Chinese Han population. We also aimed to investigate ALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma(ESCC).Methods: We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and lowincidence areas for both GCA and ESCC in China. Taq Man allele discrimination assay was used to genotype the rs671 polymorphism. χ~2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA,and multivariate ordinal logistic regression was used to analyze ALDH2 genotypic distributions among different groups.Results: Compared with ALDH2*1/*1 homozygotes, ALDH2*1/*2 and ALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population(P>0.05). Interestingly, the ratio of homozygous or heterozygous ALDH2 *2 carriers in highincidence areas for both GCA and ESCC was lower than that in low-incidence areas(P<0.001).Conclusions: Genotypes of rs671 at ALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, the ALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.

Inhibitory effects of dobutamine on human gastric adenocarcinoma

AIM:To explore the inhibitory effects of dobutamine on gastric adenocarcinoma cells.METHODS:Dobutamine was used to treat gastric adenocarcinoma cells(SGC-7901)and cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.The effects of dobutamine combined with cisplatin on cell viability were also analyzed.Cell migration was studied using the wound healing assay,and cell proliferation was analyzed using the colony formation assay.A cell invasion assay was carried out using Transwell cell culture chambers.The cell cycle and cell apoptosis were analyzed by flow cytometry.Western blot and immunocytochemistry were performed to determine the expression of Yes-associated protein(YAP)in treated cells.RESULTS:Dobutamine significantly inhibited cell growth,migration,cell colony formation,and cell invasion into Matrigel.Dobutamine also arrested the cell cycle at G1/S phase,and increased the rate of apoptosis of gastric adenocarcinoma cells.The expression ofYAP was detected mainly in the nucleus in the absence of dobutamine.However,reduced expression of phosphorylated YAP was mainly found in the cytosol following treatment with dobutamine.CONCLUSION:Dobutamine has significant inhibitory effects on gastric adenocarcinoma cells and may be used in neoadjuvant therapy not only for gastric cancer,but also for other tumors.

Alterations of tumor-related genes do not exactly match the histopathological grade in gastric adenocarcinomas

AIM:To investigate the diverse characteristics of different pathological gradings of gastric adenocarcinoma (GA) using tumor-related genes.METHODS:GA tissues in different pathological gradings and normal tissues were subjected to tissue arrays.Expressions of 15 major tumor-related genes were detected by RNA in situ hybridization along with 3' terminal digoxin-labeled anti-sense single strandedoligonucleotide and locked nucleic acid modifying probe within the tissue array.The data obtained were processed by support vector machines by four different feature selection methods to discover the respective critical gene/gene subsets contributing to the GA activities of different pathological gradings.RESULTS:In comparison of poorly differentiated GA with normal tissues,tumor-related gene TP53 plays a key role,although other six tumor-related genes could also achieve the Area Under Curve (AUC) of the receiver operating characteristic independently by more than 80%.Comparing the well differentiated GA with normal tissues,we found that 11 tumor-related genes could independently obtain the AUC by more than 80%,but only the gene subsets,TP53,RB and PTEN,play a key role.Only the gene subsets,Bcl10,UVRAG,APC,Beclin1,NM23,PTEN and RB could distinguish between the poorly differentiated and well differentiated GA.None of a single gene could obtain a valid distinction.CONCLUSION:Different from the traditional point of view,the well differentiated cancer tissues have more alterations of important tumor-related genes than the poorly differentiated cancer tissues.

Increased expression of DLX2 correlates with advanced stage of gastric adenocarcinoma

AIM:To investigate the expression of distal-less homeobox 2 (DLX2) in gastric adenocarcinoma and its clinicopathological significance. METHODS:Gastric adenocarcinoma tissues were obtained from gastrectomy specimens of 129 patients from the Department of Surgery and Pathology, the Second Affiliated Hospital of Kunming Medical University. Sixty cases of normal gastric tissues were collected from gastrectomy specimens of adjacent gastric cancer margins greater than 5 cm. Patient diagnosis was established pathologically, and no patient had received chemotherapy or radiotherapy before surgery. All tissue specimens were formalin-fixed and paraffin-embedded. Immunohistochemistry was carried out to investigate the expression of DLX2 in 129 gastric adenocarcinoma tissues and 60 adjacent normal tissues. The immunos-taining reaction was semiquantitatively evaluated based on the proportion of positive cells and the median staining intensity in normal gastric epithelial cells or tumor cells. All patients had follow-up records for more than 5 years. Correlations of DLX2 expression with clinicopathological features and prognosis of patients with gastric adenocarcinoma were analyzed. All statistical analyses were performed using the SPSS 17.0 software. RESULTS:The positive expression of DLX2 was detected in 68 (52.7%) cases of 129 gastric adenocarcinoma tissues and 14 (23.3%) cases of 60 adjacent normal tissues. The difference in DLX2 expression between gastric adenocarcinoma tissues and adjacent normal tissues was statistically significant (Ⅹ2 = 14.391, P < 0.001). Moreover, high expression of DLX2 was detected in 48 (37.2%) cases of 129 human gastric cancer tissues, but not in adjacent normal tissues. The expression of DLX2 correlated with the size of tumor (P = 0.001), depth of invasion (P = 0.008), lymph node metastasis (P = 0.023) and tumor-node-metastasis stages (P = 0.020), but was not correlated with age, gender, histological differentiation and distant metastasis. The Kaplan-Meier survival analysis revealed that survival time of patients with high DLX2 expression was significantly shorter than that with low DLX2 expression. However, the multivariate analysis showed that invasion depth (P < 0.001), lymph nodes metastasis (P = 0.001) and distant metastasis (P < 0.001) were independent prognostic factors for patients with gastric adenocarcinoma, but DLX2 expression, tumor location and tumor size were not. CONCLUSION:These results suggest that increased expression of DLX2 may correlate with the advanced stage of gastric adenocarcinoma, and it may contribute to tumor development.

Adjuvant chemotherapy,p53,carcinoembryonic antigen expression and prognosis after D2 gastrectomy for gastric adenocarcinoma

AIM:To investigate adjuvant chemotherapy,p53 and carcinoembryonic antigen(CEA)expression and prognosis after D2 gastrectomy for stageⅡ/Ⅲgastric adenocarcinoma.METHODS:A total of 286 patients with stageⅡorⅢgastric adenocarcinoma who underwent D2 radical gastrectomy between May 2007 and December 2010 were enrolled into this study.One hundred and sixty-nine of these patients received surgery plus adjuvant chemotherapy,and 117 patients received surgery alone.Tumor expression of p53 and CEA proteins in all patients was evaluated immunohistochemically and correlated with clinicopathological parameters.The Kaplan-Meier curves for overall survival(OS)and disease-free survival(DFS)with log-rank testing were used to compare the survival difference.A Cox proportional hazard regression model was used for multivariate analysis.RESULTS:Patients with adjuvant chemotherapy had a significantly better median OS(50.87 mo vs 30.73 mo,P=0.000)and median DFS(36.30 mo vs 25.60 mo,P=0.001)than patients with surgery alone in the entire cohort.Consistent results with the entire cohort were found in stageⅡ(P=0.006 and P=0.047),stageⅢ(P=0.005 and P=0.030),and stageⅢB/ⅢC patients(P=0.000 and P=0.001).The median OS and DFS advantages were confirmed by multivariate analysis(P=0.000 and P=0.008)and maintained when the analyses were restricted to fluoropyrimidine monotherapy(P=0.003 and P=0.001)and fluoropyrimidine plus platinum regimen(P=0.001 and P=0.007),however,not the fluoropyrimidine plus taxane(P=0.198 and P=0.777)or platinum plus taxane(P=0.666 and P=0.687)regimens.Median OS and median DFS did not differ significantly between the patients with p53(+)and p53(-)tumors(P=0.608 and P=0.064),or between patients with CEA(+)and CEA(-)tumors(P=0.052 and P=0.989),which were maintained when the analyses were restricted to surgery alone(p53:P=0.864 and P=0.431;CEA:P=0.142 and P=0.948),adjuvant chemotherapy(p53:P=0.802 and P=0.091;CEA:P=0.223 and P=0.946)and even different chemotherapy regimens(P>0.05).CONCLUSION:Patients after D2 gastrectomy for stageⅡ/Ⅲgastric adenocarcinoma had significantly better survival after fluoropyrimidine monotherapy and fluoropyrimidine plus platinum.p53 and CEA were not prognostic.