Cases Of Gastric Adenocarcinoma Research Articles

Alteration in the Wnt/β-catenin signaling pathway in gastric neoplasias of fundic gland (chief cell predominant) type

Gastric neoplasia of chief cell-predominant type (GN-CCP) has been reported as a new, rare variant of gastric tumor. GN-CCPs were defined as tumors consisting of irregular anastomosing glands of columnar cells mimicking chief cells of fundic gland with nuclear atypia and prolapse-type submucosal involvement. We comparatively evaluated clinicopathologic features between 31 GN-CCPs and 130 cases of conventional gastric adenocarcinoma invading into submucosa (CGA-SM) in addition to nuclear β-catenin immunolabeling and direct sequencing of members of the Wnt/β-catenin pathway, CTNNB1, APC, and AXIN, in a subset of these tumors. GN-CCP presented as small protruded lesions located in the upper third of the stomach, with minimal involvement into the submucosa and rare lymphovascular invasion. None of the lesions have demonstrated a recurrence of disease or metastasis on follow-up. Nuclear β-catenin immunolabeling was higher in GN-CCP (labeling index [LI]: median, 19.3%; high expresser [LI >30%], 7/27 cases [26%]) than CGA-SM (median LI, 14.7%; high expresser, 1/19 cases [6%]). Missense mutation of APC was observed in 1 GN-CCP but not CGA-SM. Missense or nonsense mutations of CTNNB1 and AXIN1 were higher in GN-CCPs (14.8%, both) than CGA-SMs (5.3%, both). Missense mutations of AXIN2 were higher in GN-CCPs (25.9%) than in CGA-SMs (10.5%). Overall, 14 (51.9%) of 27 GN-CCPs and 5 (26.3%) of 19 CGA-SM cases harbored at least 1 of these gene mutations. In conclusion, GN-CCPs as a unique variant of nonaggressive tumor are characterized by nuclear β-catenin accumulation and mutation of CTNNB1 or AXIN gene, suggesting activation of the Wnt/β-catenin pathway.

Decreased Expression of AZGP1 Is Associated with Poor Prognosis in Primary Gastric Cancer

Background2-Zinc-glycoprotein 1 (AZGP1) is a multidisciplinary protein that participates in many important functions in the human body, including fertilization, immunoregulation and lipid mobilization. Recently, it has been shown that AZGP1 is also involved in carcinogenesis and tumor differentiation. In this study, we investigated the expression levels and prognostic value of AZGP1 in primary gastric cancers.Methods and ResultsWe examined the expression of AZGP1 in 35 paired cancerous and matched adjacent noncancerous gastric mucosa tissues by real-time quantitative RT-PCR (qRT-PCR) and western blotting. Furthermore, we analyzed AZGP1 expression in 248 patients who underwent resection procedures between 2005 and 2007 using immunohistochemistry. The relationships between the AZGP1 expression levels, the clinicopathological factors, and patient survival were investigated. AZGP1 expression was significantly reduced at both the mRNA (P = 0.023) and protein levels (P = 0.019) in tumor tissue samples, compared with expression in matched adjacent non-tumor tissue samples. The immunohistochemical staining data showed that AZGP1 expression was significantly decreased in 52.8% (131/248) of gastric adenocarcinoma cases. Clinicopathological analysis showed that the reduced expression of AZGP1 was significantly correlated with tumor location (P = 0.011), histological grade (P = 0.005) and T stage (P = 0.008). Kaplan–Meier survival curves revealed that the reduced expression of AZGP1 was associated with a poor prognosis in gastric adenocarcinoma patients (P = 0.009). Multivariate Cox analysis identified AZGP1 expression was an independent prognostic factor for overall survival of gastric adenocarcinoma patients (HR = 1.681, 95% CI = 1.134–2.494, P = 0.011).ConclusionsOur study suggests that AZGP1 might serve as a candidate tumor suppressor and a potential prognostic biomarker in gastric carcinogenesis.

The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis

A subset of gastric (intestinal-type) and esophageal (Barrett) adenocarcinoma features HER2 protein overexpression. Consistent evidence demonstrates that microRNAs have a major role in HER2 (dys)regulation. MiR-125a-5p and miR125b expressions were tested in the spectrum of lesions in the gastroesophageal carcinogenic cascade, also correlating miR-125a-5p/125b levels with HER2 status. MiR-125a-5p and miR-125b expression (quantitative reverse transcriptase polymerase chain reaction [qRT-PCR]) and HER2 status (immunohistochemistry [IHC] and chromogenic in situ hybridization [CISH]) were assessed in a series of 90 biopsy samples spanning the whole histologic spectrum of gastric and esophageal carcinogenesis. To support the obtained results, the qRT-PCR levels of microRNAs and their expression (in situ hybridization) were tested in an adjunctive series of gastric and esophageal adenocarcinoma, including (IHC/CISH validated) HER2-negative and HER2-positive cases. Both miR-125a-5p and miR-125b levels were significantly down-regulated throughout the gastric and esophageal carcinogenic cascade. HER2 status (IHC and CISH) correlated inversely with miR-125 expression (qRT-PCR and in situ hybridization). Dysregulation of miR-125a-5p/125b and HER2 is an early event in the gastric (intestinal-type) and esophageal (Barrett) oncogenesis. In both oncogenetic cascades, miR-125 expression correlates inversely with HER2 status. MiR-125a-5p/125b can be considered among the therapeutic targets in HER2-positive esophageal and gastric adenocarcinoma.

Opium: an emerging risk factor for gastric adenocarcinoma.

Opium use has been associated with higher risk of cancers of the esophagus, bladder, larynx, and lung; however, no previous study has examined its association with gastric cancer. There is also little information on the associations between hookah (water pipe) smoking or the chewing of tobacco products and the risk of gastric cancer. In a case-control study in Golestan Province of Iran, we enrolled 309 cases of gastric adenocarcinoma (118 noncardia, 161 cardia and 30 mixed-location adenocarcinomas) and 613 matched controls. Detailed information on long-term use of opium, tobacco products and other covariates were collected using structured and validated lifestyle and food frequency questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models. Opium use was associated with an increased risk of gastric adenocarcinoma, with an adjusted OR (95% CI) of 3.1 (1.9-5.1), and this increased risk was apparent for both anatomic subsites (cardia and noncardia). There was a dose-response effect, and individuals with the highest cumulative opium use had the strongest association (OR: 4.5; 95% CI: 2.3-8.5). We did not find a statistically significant association between the use of any of the tobacco products and risk of gastric adenocarcinoma, overall or by anatomic subsite. We showed, for the first time, an association between opium use and gastric adenocarcinoma. Given that opium use is a traditional practice in many parts of the world, these results are of public health significance.

Dietary Intake of Lignans and Risk of Esophageal and Gastric Adenocarcinoma: A Cohort Study in Sweden

High intake of phytoestrogen lignans has been found to be associated with decreased risk of esophageal adenocarcinoma in our previous population-based case-control study in Sweden. To further evaluate this possible association, we tested the hypothesis of an inverse association between dietary lignan intake and risk of esophageal and gastric adenocarcinoma using a prospective design. In a population-based cohort study in Sweden, 81,670 participants who were cancer-free at baseline were followed up during 1998 to 2009. All participants completed a 96-item food frequency questionnaire (FFQ), which was used to assess dietary exposure to lignans (secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, medioresinol, and syringaresinol). All cases of esophageal, gastroesophageal junctional, and gastric adenocarcinoma were identified through linkage to the Swedish Cancer Register. Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CI), with adjustment for potential confounding factors. During an average follow-up of 9.9 years, a total of 211 cases were identified, including 83 cases of esophageal or junctional adenocarcinoma, and 128 cases of gastric adenocarcinoma. There was no statistically significant association between dietary intake of lignans and any of the studied adenocarcinomas. Compared with participants in the lowest quartile of lignan intake, the adjusted HR of the highest quartile was 0.96 (95% CI, 0.46-2.00; P(trend) = 0.70) for adenocarcinoma of the esophagus or gastroesophageal junction, and 0.89 (95% CI, 0.52-1.55: P(trend) = 0.78) for gastric adenocarcinoma. No clear support for a protective role of dietary intake of lignans in the development of esophageal or gastric adenocarcinoma was found.

A public hospital experience with young gastric cancer patients.

30 Background: Recent literature has reported an increased incidence in the United States of node positive and metastatic disease in young patients with gastric adenocarcinoma. The purpose of this study was to investigate the effect of age (≤40 years) on patients with gastric adenocarcinoma at a large urban public institution. Methods: A total of 520 cases of gastric adenocarcinoma treated between 1995 and 2012 were identified. Information was gathered from the medical record including age at presentation, stage at presentation, pathological type of GC, treatment received, and mortality data. Descriptive statistics were used to analyze the data. Survival was analyzed using the Kaplan-Meier method. Comparisons were made using the log-rank test. Results: The mean age at diagnosis was 56 years. 64 patients (12%) were identified as ≤40 years old. 57 of 64 (89%) of the young age group presented with stage III or IV disease, compared with 75% of patients >40 years of age (p=0.014). For patients ≤40 years old, 38% underwent an operation with curative intent, which was comparable to 39% in patients >40 years old. Of patients who underwent surgery, only 33% (10 of 30) ≤40 years old received an R0 resection compared to 110 of 184 (60%) in those >40 years old (p=0.007). The overall median survival was 5 months with one-year survival of 24% for the young patients and a median of 7.8 months with 39% one-year survival for the older patients (p=0.016). Conclusions: There is a decreased awareness and therefore suspicion of the diagnosis of gastric cancer in young patients (≤40 years of age). For this reason, young patients with gastric adenocarcinoma may present with more advanced disease than older patients. Surgical exploration was often futile, and survival was especially poor in young patients likely due to the more advanced nature of their disease at diagnosis.

The impact of race on gastric cancer outcomes in the United States.

83 Background: Disparities in gastric cancer outcomes are well-documented. We evaluate the association of race with gastric cancer outcomes using a diverse database of patients in the U.S. Methods: SEER was queried for gastric adenocarcinoma cases from 2004-2008, excluding cardia. Logistic (LR) and Cox regressions were used for analyses. Results: 9,440 cases were analyzed: 4,134 (43.8%) Whites (W), 2,015 (21.3%) Asian-American Pacific Islanders (AP), 1,826 (19.3%) Hispanics (H), and 1,465 (15.5%) Blacks (B). Presentation: Average age was 70.1. B, H, and AP were more likely than W to present younger. AP were more likely and H less likely than W to present at a lower stage. B were more likely to have a lower grade. No differences in gender were seen. Treatment: Compared to W, AP were more likely to have surgery. AP, H, and B were more likely to receive radiation (XRT). AP and H had increased odds of ≥15 lymph nodes examined (LNE). Survival: AP and H had improved but B had worse survival compared to W when stratified by receipt of surgery, XRT, and stage and adjusted for age, gender, LNE, anatomic site, and grade. Conclusions: AP were more likely to present with lower stage, have surgery, XRT, ≥15 LNE, and highly significantly better survival than W. H were more likely to present younger but with higher stage, have ≥15 LNE, XRT, and better survival. For B there were no differences in stage or receipt of surgery, though there were increased odds of XRT but had worse survival. These racial disparities in gastric cancer suggest potential differences in tumor or host biology and quality of treatment that impact outcomes and merit further study. [Table: see text]

Decreased Expression of Transcription Elongation Factor A-Like 7 Is Associated with Gastric Adenocarcinoma Prognosis

BackgroundWe sought to investigate the expression levels and prognosis value of TCEAL7 in primary gastric cancer.Methods and ResultsWe investigated TCEAL7 and other homologous five members of the TCEAL family expression in normal gastricepithelial cell line and gastric cancer cell lines using real-time quantitative PCR. Furthermore, we examined the expression of TCEAL7 in 39 paired cancerous and matched adjacent noncancerous gastric mucosa tissues by real-time quantitative PCR and western blotting. Moreover, we analyzed TCEAL7 expression in 406 gastric cancer patients using immunohistochemistry. The relationships between the TCEAL7 expression levels, the clinicopathological factors, and patient survival were investigated. RT- qPCR data showed that mRNA expression level of TCEAL7 was significantly lower in the gastric cancer cell lines comparing with the levels of other five members of the TCEAL family. Results also revealed decreased TCEAL7 mRNA (P = 0.025) and protein (P = 0.012) expression in tumor tissue samples compared with matched adjacent non-tumor tissue samples. Immunohistochemical staining data showed that TCEAL7 expression was significantly decreased in 43.3% of gastric adenocarcinoma cases. The result also showed that the low TCEAL7 expression was significantly correlated with female, larger tumor size, higher histological grade and worse nodal status. Kaplan–Meier survival curves revealed that the reduced expression of TCEAL7 was associated with a poor prognosis in gastric adenocarcinoma patients (P<0.001). Based on a univariate analysis that included all 406 patients, TCEAL7 expression was found to have statistically significant associations with overall survival (P<0.001). Multivariate analysis also demonstrated that TCEAL7 expression (P = 0.009), age, tumor size, histological grade, lymphovascular invasion, T stage, N stage and M stage were independent risk factors in the prognosis of gastric cancer patients.ConclusionsOur study suggests that TCEAL7 might serve as a candidate tumor suppressor and a potential prognostic biomarker in gastric carcinogenesis.

That dyspepsia in the young could be cancer

Malignant tumour of the stomach is not common in young adults. When it does occur, it is associated with a high morbidity and mortality. The objective of this report is to document our experience with three cases of gastric adenocarcinoma in young adult Nigerians seen over a period of 18 months in our centre.

Goiter Frequency Is More Strongly Associated with Gastric Adenocarcinoma than Urine Iodine Level

PurposeWe designed our study to evaluate the hypothesis that gastric cancer is correlated with iodine deficiency or thyroid dysfunction.Materials and MethodsWe investigated the total body iodine reserve, thyroid function status and autoimmune disorder in 40 recently diagnosed gastric adenocarcinoma cases versus 80 healthy controls. The participants came from a region with high gastric cancer rate but sufficient iodine supply due to salt iodination. The investigation included urine iodine level, thyroid gland clinical and ultrasonographic examination, and thyroid function tests.ResultsGoiter was detected more frequently in the case group (P=0.001); such a finding, however, was not true for lower than normal urine iodine levels. The free T3 mean level was significantly lower in the case group compared to the control group (P=0.005).ConclusionsThe higher prevalence of goiter rather than low levels of urinary iodine in gastric adenocarcinoma cases suggests that goiter, perhaps due to protracted but currently adjusted iodine deficiency, is more likely to be associated with gastric adenocarcinoma compared to the existing iodine deficiency itself.

Concomitant Gastrointestinal Stromal Tumor of the Stomach and Gastric Adenocarcinoma in a Patient with Billroth 2 Resection

Background. With this study we focus on the etiopathogenesis and on the therapy of the simultaneous occurrence of Gastric gastrointestinal stromal tumor (gGIST) and adenocarcinoma of the stomach in a patient with Billroth II gastric resection (BIIGR). We report the first case of this event and a review of the literature. Methods. A 70-year-old man with a BIIGR, affected by adenocarcinoma of the stomach, was successfully treated with total gastrectomy. The histological examination showed a gastric adenocarcinoma with a synchronous GIST sized 2 cm and S-100, CD117, and CD34 positive. The mutation of PDGFR gene was detected. Discussion. This tumor is a rare mesenchymal neoplasm of the gastrointestinal tract. Few cases of synchronous gastric adenocarcinoma and GIST are observed in the literature and no case in patients with BIIGR. Various hypotheses have been proposed to explain this occurrence. It is frequently attributed to Metallothioneins genes mutations or embryological abnormalities, but this has not been proven yet. We suggest a hypothesis about the etiopathogenesis of this event in a BIIGR patient. Conclusion. GIST may occur synchronously with gastric adenocarcinoma. This simultaneous occurrence needs more studies to be proven. The study of Cajal cells' proliferation signalling is crucial to demonstrate our hypotesis.

Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer. We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study. A total of 120,852 men and women aged 55-69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adenocarcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis. Positive associations were observed between N-nitrosodimethylamine intake and ESCC risk (HR for 0.1-μg/d increase in intake: 1.15; 95% CI: 1.05, 1.25; P-trend = 0.01 based on tertiles of intake) and GNCA risk (1.06; 95% CI: 1.01, 1.10; P-trend = 0.09) in men. ESCC risk was associated with nitrite intake (HR for 0.1-mg/d increase: 1.19; 95% CI: 1.05, 1.36; P-trend = 0.06) and heme-iron intake (HR for 1-mg/d increase: 1.83; 95% CI: 0.98, 3.39; P-trend = 0.03). Among women, exposure levels were lower, and we found no convincing positive associations. These results suggest that N-nitroso compounds may influence the risk of ESCC in men, but there are no clear associations for other esophageal and gastric subtypes.

Clonality analysis of neuroendocrine cells in gastric adenocarcinoma

To achieve a better understanding of the origination of neuroendocrine (NE) cells in gastric adenocarcinoma. 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. 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 and 10. 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. NE and the gastric adenocarcinoma cells may mainly derive from the same stem cells, but the remaining cases showing different origin needs further investigation.

Gastric cancer incidence estimation in a resource-limited nation: use of endoscopy registry methodology

Cancer epidemiology is challenging in developing nations, in the absence of reliable pathology-based cancer registries. Clinical experience suggests that the incidence of gastric cancer is high in Honduras, in contrast to the limited available national statistics at the time of study initiation (IARC GLOBOCAN 2002: males 15.2, females 10.8). We estimate the incidence of gastric cancer for Honduras using an endoscopy registry as a complimentary resource. We conducted a retrospective analysis of incident noncardia gastric adenocarcinoma cases in western Honduras for the period 2000-2009. This region is well circumscribed geopolitically with a single district hospital and established referral patterns, to provide a unique epidemiological niche to facilitate estimation of incidence rates. A prospective, comprehensive database of all endoscopy procedures from this hospital was utilized at the primary data source. The catchment area for gastroenterology services for the at-risk population was validated by calculating the overall endoscopy utilization rates for each municipality in western Honduras. Incident cases of gastric adenocarcinoma were determined by the endoscopic diagnosis. Pathology services are not financed by the Ministry of Health, and histology data were incorporated when available. Population statistics were obtained from the Honduras National Statistics Institute (INE). Age-standardized incidence rates (ASIRs) were calculated using world standard population fractions. The catchment area for western Honduras was validated with the municipality threshold of 30 endoscopies per 10(6) person-years, with inclusion of a total of 40 municipalities. In the western Honduras catchment area, there were 670 incident cases (439 M, 231 F) of noncardia gastric adenocarcinoma during the study decade 2000-2009. Notably, 67 (10.0 %) and 165 (24.6 %) of cases were under the ages of 45 and 55, respectively. The case-finding rate was 5.1 endoscopies performed for each new diagnosis of gastric cancer. The ASIRs for the decade were 30.8 for males and 13.9 for females. Clinically, 60.3 % of gastric cancers were Borrmann type 3 (ulcerated mass), and evidence of advanced disease with pyloric obstruction was common (35.2 %). Subtypes by the Lauren classification were distributed among diffuse (56 %), intestinal (34 %), and indeterminate (9.9 %), in subjects with available pathology (526/670). The endoscopy procedure registry may serve as a complimentary data resource for gastric cancer incidence estimation in resource-limited nation settings wherein pathology services and cancer registries are absent. The results remain an underestimation in this setting due to the challenges of access to care and related factors. The methodology helps to more fully characterize the high incidence of gastric cancer in western Honduras and this region of Central America and demonstrate the need for additional epidemiology research, and interventions focused on prevention and treatment.

Polymorphisms in ERCC1 and XPF genes and risk of gastric cancer in an eastern Chinese population.

BackgroundInherited functional single nucleotide polymorphisms (SNPs) in DNA repair genes may alter DNA repair capacity and thus contribute to cancer risk.MethodsThree ERCC1 functional SNPs (rs2298881C>A, rs3212986C>A and rs11615G>A) and two XPF/ERCC4 functional SNPs (rs2276466C>G and rs6498486A>C) were genotyped for 1125 gastric adenocarcinoma cases and 1196 cancer-free controls by Taqman assays. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate risk associations, and false-positive report probabilities (FPRP) were calculated for assessing significant findings.Results ERCC1 rs2298881C and rs11615A variant genotypes were associated with increased gastric cancer risk (adjusted OR = 1.33, 95% CI = 1.05–1.67 for rs2298881 AC/CC and adjusted OR = 1.23, 95% CI = 1.05–1.46 for rs11615 AG/AA, compared with their common genotype AA and GG, respectively). Patients with 2–3 ERCC1 risk genotypes had significant increased risk (adjusted OR = 1.56, 95% CI = 1.27–1.93), compared with those with 0–1 ERCC1 risk genotypes, and this risk was more significantly in subgroups of never drinkers, non-gastric cardia adenocarcinoma (NGCA) and clinical stage I+II. All these risks were not observed for XPF SNPs.ConclusionsThese findings suggest that functional ERCC1 SNPs may contribute to risk of gastric cancer. Larger and well-designed studies with different ethnic populations are needed to validate our findings.

Prospective cohort study of metabolic risk factors and gastric adenocarcinoma risk in the Metabolic Syndrome and Cancer Project (Me-Can)

Little is known about the association between the metabolic syndrome (MetS) and the risk of gastric adenocarcinoma. The aim of this study was to investigate whether metabolic risk factors, together or combined, were associated with the risk of gastric adenocarcinoma. The Metabolic Syndrome and Cancer Project (Me-Can) is a pooling of prospective cohorts in Austria, Norway, and Sweden with information on blood pressure, lipids, glucose, and BMI available in 578,700 individuals. Cox proportional hazards analysis was used to calculate hazard ratio (HR) of gastric adenocarcinoma using metabolic risk factors categorized into quintiles and transformed into z-scores (with mean=0 and SD=1). The standardized sum of all z-scores created a composite MetS score. In total, 1,210 incident cases of gastric adenocarcinoma were identified. Glucose was significantly associated with the risk of gastric adenocarcinoma [calibrated HR 1.58 (1.14-2.20) per one unit increment in z-score] in women. There was a statistically significant association between triglycerides and risk of gastric adenocarcinoma per mmol increment in triglycerides [HR 1.20 (1.06-1.36) per mmol] but not for the adjusted z-score in women. There were no significant association between any metabolic factors and gastric cancer among men. The composite MetS score was associated with the risk of gastric adenocarcinoma in women [HR 1.18 (1.00-1.38) per one unit increment in z-score] but not in men. Glucose and high levels of the composite MetS score were associated with an increased risk of gastric adenocarcinoma in women but not in men.

Expression of Yes-associated protein in gastric adenocarcinoma and effects of Yes-associated protein knockdown on proliferation and metastasis of gastric cancer cells

Objective To examine the expression of Yes-associated protein (YAP) in human gastric adenocarcinomas,gastric adenomas and normal gastric mucosa tissues,and further explore the effects and molecular mechanisms of YAP on proliferation and metastasis of gastric cancer cells.Methods The expression of YAP in 78 cases of gastric adenocarcinomas,39 cases of gastric adenomas and 46 cases of normal gastric mucosa tissues was detected by using immunohistochemistry and real-time polymerase chain reaction (PCR).In vitro human gastric cancer SGC-7901 cells were stably transfected with lentivirus-mediated YAP small hairpin RNA (shRNA),and the expression levels of proliferating cell nuclear antigen (PCNA) and metalloproteinase-2 (MMP-2) were detected by using Western blotting.The proliferative activity and metastatic capability of gastric cancer cells were evaluated by methyl thiazol tetrazolium (MTT) and Transwell assays.Results The expression of YAP was observed in 69.23％ gastric adenocarcinoma tissues,and its mRNA expression level in gastric adenocarcinoma (1.74 ± 0.46) was significantly increased as compared with that in normal gastric mucosa (0.33 ± 0.15) and gastric adenoma (0.42 ±0.20).Knockdown of YAP by shRNA could down-regulate the expression of PCNA and MMP-2,and inhibit the proliferation and metastasis of gastric cancer cells.Conclusion YAP is strongly expressed in gastric adenocarcinoma,and knockdown of YAP inhibits proliferation and metastasis of gastric cancer cells. Key words: Gastric carcinoma; Yes-associated protein; Small hairpin RNA; Proliferation; Metastasis

Abstract A99: Dietary N-nitroso compounds, endogenous nitrosation and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

Abstract Background: Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but evidence for their role from population studies is scarce for esophageal, and inconsistent for gastric cancer. Objective: We studied the relationship between the risk of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite and nitrate in The Netherlands Cohort Study. Methods: 120 852 men and women aged 55-69 years were recruited in 1986, and diet, based on a 150-item food frequency questionnaire, as well as other risk factors were assessed. The cohort was followed for 16.3 years, and 110 esophageal squamous cell carcinomas, 151 esophageal adenocarcinomas, 166 gastric cardia adenocarcinomas, and 497 gastric non-cardia adenocarcinoma cases were analyzed along with 4032 subcohort members in a case-cohort analysis. Results: There were positive associations between N-nitrosodimethylamine intake and esophageal squamous cell carcinoma and gastric non-cardia adenocarcinoma risk in men (hazard ratio (HR) for 0.1 μg/day increase in intake: 1.15 [95% confidence interval (CI): 1.05-1.25; P(trend): 0.01] and 1.06 [95%CI: 1.01-1.10; P(trend): 0.09], respectively). Esophageal squamous cell carcinoma risk was associated with nitrite and heme iron intake (HR for 0.1 mg/day increase in nitrite intake: 1.19 [95%CI: 1.05-1.36; P(trend): 0.06] and for 1 mg/day heme iron intake: 1.83 [95%CI: 0.98-3.39; P(trend): 0.03]). Among women, exposure levels were lower, and we found a positive association only between N-nitrosodimethylamine and esophageal squamous cell carcinoma risk (HR for 0.1 μg/day increase: 1.34 [95%CI: 1.04,1.71; P(trend):0.57]). Conclusion: These results suggest that N-nitroso compounds and their precursors may influence the risk of esophageal squamous cell carcinoma. Citation Format: András P. Keszei, R Alexandra Goldbohm, Leo J. Schouten, Paula Jakszyn, Piet A. van den Brandt. Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A99.

Long-Term Survivors of Gastric Cancer: A California Population-Based Study

In the United States, gastric cancer is rapidly fatal with a 25% 5-year survival. Of the few patients who survive, little is known about their demographic, clinical, and tumor characteristics. Data regarding all cases of gastric and gastroesophageal junction (GEJ) adenocarcinoma diagnosed in California between 1988 and 2005 were obtained from the California Cancer Registry, a member of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. A Cox proportional hazards model was constructed to understand the independent relationships of patient demographic, disease, and treatment factors with survival. We identified 47,647 patients diagnosed with gastric or GEJ cancer. Of those, only 9,325 (20%) survived at least 3 years. Variables associated with longer survival were localized stage (hazard ratio [HR], 0.20), surgery with diagnosis in 2002 or later (HR, 0.34), surgery with diagnosis in 2001 or before (0.37), regional stage (HR, 0.53), chemotherapy (HR, 0.56), intestinal histology (HR, 0.74), well- or moderately differentiated tumors (HR, 0.76), radiation (HR, 0.80), Asian/Pacific Islander race (HR, 0.81), treatment at an academic hospital (HR, 0.85), fundus/body/antrum location (HR, 0.90), highest socioeconomic status quintile (HR, 0.91), female sex (HR, 0.92), Hispanic race (HR, 0.92), and hospital size more than 150 beds (HR, 0.94). Kaplan-Meier curves showed longer median disease-specific survival (DSS) in patients with tumors originating in the fundus/body/antrum compared with esophagus/cardia (13.4 v 10.8 months). Intestinal histology had significantly longer median DSS (28.9 months) compared with other (11.0 months) or diffuse (10.1 months) histology. Patients who survive gastric and GEJ cancer more than 3 years after diagnosis have demographic and pathologic characteristics distinct from those who do not survive.

Perineural Invasion Independent Prognostic Factors in Patients with Gastric Cancer Undergoing Curative Resection

The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated but not clearly clarified. The objective of our study was to investigate the role of PNI as prognostic factor in patients undergoing curative surgical resection and without distant metastasis in comparison with other clinicopathological factors. Between 2001 and 2010, 287 cases of gastric adenocarcinoma underwent radical gastrectomy recorded in hospital based registries. PNI was assessed as positive when cancer cells were seen in the perinerium or neural fascicles intramurally. Categorical and continuous variables were summarized using descriptive statistics and compared using chi-square and Mann-Whitney U tests, respectively. Cancer related survival rates were estimated by the Kaplan-Meier method. PNI was positive in 211 of 287 cancers (73%), with a positive relation to lymph node metastases and advanced stage (p=0.0001, p=0.0001, respectively), mural invasion, and lymphatic and blood vessel invasion (p=0.0001, p=0.0001, respectively). The median survival of the PNI positive patients was significantly shorter than that of their PNI negative counterparts (24.1 versus 38.2 months, p=0.008). In the multivariate analysis, we detected PNI was an independent prognostic factor (p=0.025, HR=1.21, 95% CL 1.08-2.3) along with classical clinicopathological variables such as lymph node involvement (p=0.001), pT stage (p=0.03), and LVI (p=0.017), but not age, gender, tumour localization, stage, histologic type, and surgery procedure. PNI positivity in gastric cancers was related mural invasion, lymph node involvement, advanced stage and lymphatic and venous blood vessels. The presence of PNI appeared as an independent prognostic factor on survival on multivariate analysis, not influenced by tumor stage, lymph node metastases and other classical factors.