Lauren Histologic Type Research Articles

Epstein-Barr Virus and Clinico-Endoscopic Characteristics of Gastric Remnant Cancers Compared to Proximal Non-Remnant Cancers: A Population-Based Study.

Epstein-Barr virus (EBV) is associated with 5-10% of gastric cancers and is recognized as a distinct molecular subtype. EBV positivity is particularly high in gastric remnant cancer (GRC), which may inform the mode of clinical presentation and findings at endoscopy. Most data are from the East, and the question remains how this applies to a Western cohort. We conducted a population-based study in Central Norway, 2001-2016. Patients with GRC (n = 78) and patients with non-GRC proximally located cancer and available tissue for EBV status (n = 116, control group) were identified from the Norwegian Cancer Registry. Relevant data were collected from the individual patient journals. EBV status was assessed using in situ hybridization. The median latency time from the distal gastrectomy to GRC was 37.6 (range 15.7-68.0) years. GRC more often presented with GI bleeding, 31.0% vs. 16.1%, p = 0.017, and at endoscopy more seldom with an ulcer, 19.7% vs. 38.2%, p = 0.012, or a tumour, 40.8% vs. 66.4%, p < 0.001. For GRC, 18.7% were EBV-positive compared to 6.0% among the controls, p = 0.006. EBV status was not associated with patient age, sex, or Lauren histological type. No difference in long-term survival rates between GRC and controls was found or between EBV-positive vs. -negative GRCs. In conclusion, a higher proportion of GRC cases, compared to controls, are EBV positive, indicating different causative factors. The mode of clinical presentation and findings at endoscopy were more subtle in the patients with GRC.

The Contribution of the Hunger Hormone Leptin in the Aetiology of Postoperative Anorexia after Laparoscopic and Open Gastrectomy in Gastric Cancer Patients.

Background: Laparoscopic surgery produces lesser postoperative inflammation with a smaller cytokine and leptin response, and might thus reduce postoperative anorexia compared with open surgery. The aim of the present study was to determine the role of serum leptin in postoperative anorexia after laparoscopic gastric cancer surgery. Methods: Fifty-four consecutive patients with adenocarcinoma of the stomach were operated on either with open or laparoscopic surgery. Correlations were determined between the serum levels of leptin, clinico-pathological characteristics, serum haemoglobin, and albumin. Results: Serum leptin levels on day seven were correlated significantly to gender (p = 0.004), body mass index (BMI) (p = 0.002), and tumour grade (p = 0.033). In the patients with C-reactive protein (CRP) < 100 mg/L (n = 46) the leptin levels on day seven were significantly lower after the laparoscopic operation (p = 0.042) and in patients with lower BMI (p = 0.001). The linear regression model determined a significant correlation between the relative concentration of leptin on day seven and laparoscopic surgery (Beta−0.688; p < 0.0001), gender, BMI, location of the tumour, T stage, N stage, perioperative therapy, tumour grade, perineural invasion, Lauren histological type, and ulceration. In patients with CRP levels below 100 mg/mL, the serum level of albumin on day seven after surgery was significantly higher in patients after laparoscopic surgery. Conclusion: Laparoscopic surgery produced significantly lower relative leptin concentrations on day seven, and higher serum albumin levels in the subgroup with CRP levels below 100 mg/L at discharge. These results suggested that laparoscopic gastric cancer surgery might reduce postoperative leptin response, leading to a better nutritional status at discharge compared with open surgery.

The identification of tumor-infiltrating lymphocytes in patients with stomach cancer

Background. Stomach cancer (SC) is the 6th most common neoplasm among cancers (1 033 701 cases; 5.7%) and the 3rd most deadly cancer worldwide for men and women (782 685 deaths, 8.2%). SC therapy is a complex treatment associated with surgery, adjuvant chemotherapy, targeted therapy and immunotherapy with checkpoint inhibitors, nowadays. Despite the fact that the SC understanding has significantly increased within recent years, the prognosis still remains poor. In addition, very often the patients with the same stage of SC according to the international TNM classification of malignant tumors have different overall survival. Therefore, in order to improve survival rates, is necessary to understand the mechanisms of disease progression and to find new effective predictive factors. Besides many SC predictive factors, such as clinical and morphological characteristics (Lauren histologic type of tumor, degree of differentiation), biomarkers, deficient mismatch repair (dMMR), we have also revealed the positive correlation between the degree of tumor infiltration of tumor-infiltrating lymphocytes (TILs), especially with the spatial location of cell types (intratumoral or stromal cells), and the survival indicators of the patients with malignant neoplasms, recently. Moreover, TILs are the most significant predictive factors in patient survival rates than the TNM classification. At the same time, TILs predictive role in SC is still not clearly defined. Thus, the understanding of the degree of tumor infiltration of TILs depending on the spatial location would allow to determine the predictive significance, as well as to determine the direction of the immune reactions generating in patients with SC at the tissue level, depending on the risk and probability of progression. Aim. To study the predictive significance of intratumoral and stromal CD4+TILs, CD8+TILs and CD4+/CD8+TILs in patients with gastric adenocarcinoma. Materials and methods. From 2017 to 2018, 45 previously untreated patients with gastric adenocarcinoma (25 patients with stages IIII, 20 patients with stage IV) received surgical/combined treatment or independent chemotherapy, respectively, at the Blokhin National Medical Research Center of Oncology. The histological material was carried out before the treatment. Intratumoral (iTILs) and stromal (sTILs) values of CD4+TILs, CD8+TILs, CD4/CD8+TILs and the predictive significance in respect of overall survival and progression-free survival (PFS) were studied. Results. During the observation period (16.46.2 months) CD4+/CD8+iTILs were factors of poor prognosis concerning PFS in patients of the first group (p=0.035; odds ratio OR 3.264, 95% confidence interval CI). We also identified the statistically significant decrease in CD4+iTILs, CD8+iTILs, CD4+/CD8+iTILs and the absence of CD4+sTILs, CD8+sTILs, CD4+/CD8+sTILs in patients with metastatic SC (р=0.0003; р=0.000004; р=0.00001). Conclusion. The results show the positive predictive significance of CD4+sTILs, CD8+sTILs, CD4+/CD8+sTILs. At the same time, the increase of CD4+/CD8+iTILs reduces the PFS in patients with early and locally advanced SC.

The application of 18F-FDG-PET/CT in gastric cancerstaging and factors affecting its sensitivity.

To evaluate the accuracy offluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), to correctly determine initial tumor stage in treatment-naive gastric cancer patients and to analyze the factors influencing the risk of false negative results. The baseline 18F-FDG PET/CT scans of 111 previously untreated gastric cancer patients were retrospectively assessed. Sensitivity, specificity, positive (PPV) and negative prediction value (NPV) were evaluated. An array of clinical, pathological and metabolic variables was analyzed to identify factors contributing to the risk of a false positive (FP) and false negative (FN) PET/CT result in detecting primary and metastatic tumor sites. The sensitivity, specificity, PPV and NPV of PET/CT to visualize distant metastases were 76.4%; 86.7%; 83% and 81.2%, respectively. In 13 (11.7%) patients the PET/CT exam was able to identify metastatic sites not recognized in radiographic staging, significantly altering the initially planned management. Of 64 PET/CT studies negative for distant metastases, 12 (18.75%) were clinically confirmed to be false negative. The risk of acquiring a FN result for primary tumor was 10.8% (12/111) and the overall risk of any FN readout for either primary and metastatic sites was 18.9% (21/111). The factors that contributed to increased probability of a FN result for primary tumor detection were early primary tumor stage T1-T2 (+16.2%; χ2=5.0, P=0.025), female sex (+10.1%; χ2=5.71, P=0.017) and neutrophil count below 4.2k/μL (9.7%; χ2=6.1, P=0.014). Patients with non-intestinal Lauren histologic type (+18.7%; χ2=8.9, P=0.003) or signet-ring/mucinous carcinoma (+9.6%; χ2=7.7, P=0.005) had increased probability of PET/CT being unable to identify their distant metastases. Women and patients with low neutrophil count featured borderline insignificantly increased percentage of non-intestinal tumor histology (P=0.07 and P=0.057, respectively). Fluorine-18-FDG PET/CT is a valuable diagnostic method in gastric cancer patients which significantly contributes to determining the TNM stage and thus helps choose correct patient management. Histology and primary tumor stage as well as patient cohorts in which these factors may vary should be considered when evaluating results to decrease a chance of a false negative readout.

Frequency and Clinical Characteristics of Unselected Korean Gastric Cancer Patients with a Germline CDH1 V832M Mutation

Background: Germline mutations in CDH1 are associated with hereditary and early onset- diffuse gastric cancer. However, the frequency of CDH1 germline mutation in unselected gastric cancer cases is not well established.Aim: The aim of this study was to investigate the frequency and clinical characteristics of germline CDH1 V832M mutation carriers in unselected Korean gastric cancer cases.Methods: Direct sequencing was performed to determine the presence of CDH1 V832M in 305 unselected Korean gastric cancer patients. Lauren's histologic type, family history of gastric cancer, and age of cancer diagnosis were compared between V832M carriers and non-carriers.Results: In the study population, seven gastric cancer patients (7/305, 2.29%) were found to have the CDH1 V832M mutation. The CDH1 V832M mutation carrier state was not significantly associated with phenotypes including Lauren's histologic type, family history of gastric cancer, age of cancer diagnosis, and other cancer history in a patient.Conclusion: This study demonstrates that the germline CDH1 V832M mutation is common in sporadic, late onset, and intestinal type gastric cancer as well as familial, early onset, and diffuse type gastric cancer. Our finding suggests that guidelines for managing CDH1 mutation carriers should be refined through additional data on penetration according to CDH1 mutation type in sporadic cases.

Diet and gastric cancer

Context: Gastric cancer is the fifth most common malignancy, with a high incidence in Eastern Asian countries. Diet is an important risk factor in the genesis of gastric cancer, and the fact that it is modifiable warrants it to be studied extensively in relation to various clinicopathological parameters of gastric cancer. Aims: The present study was undertaken to study the dietary habits (vegetarian/nonvegetarian) among gastric carcinoma patients in the Indian context. Materials and Methods: We studied 100 consecutive cases of gastric carcinoma excluding tumors at gastroesophageal junction. Clinical data regarding food habits in the patients were collected by personal enquiry. Pathological characteristics including size, site, gross appearance, Lauren's histological type, and the World Health Organization (WHO) histological type were noted. Data analysis was done using Chi-square test. Results: Sixty-nine percent of gastric cancer patients were vegetarians and 31% were nonvegetarians. Statistically significant association between nonvegetarian diet and gastric cancer location at the lesser curvature was found (P ≤ 0.001). No statistically significant association between diet and gross appearance, Lauren's, and WHO histological type of gastric cancer was found. Conclusions: For anatomical locations, most gastric cancers located at lesser curvature had been developed among nonvegetarian patients, whereas we did not observe diet to be related to gross appearance and histological type of gastric carcinoma.

Lauren Histologic Type Is the Most Important Factor Associated With Pattern of Recurrence Following Resection of Gastric Adenocarcinoma

To examine sites of initial recurrence in patients after resection of gastric and gastroesophageal junction Siewert II/III adenocarcinoma (GA). There are few recent studies on recurrence for Western patients following potentially curative resection of GA. A review of a prospectively maintained, single institution database was performed. Clinicopathologic factors, site(s) of initial recurrence, disease-free survival, and overall survival were examined. From January 2000 to June 2010, 957 patients underwent potentially curative resection for GA, 435 patients (46%) had recurrent disease, and complete data on recurrence site(s) could be obtained in 386 patients. Tumors were Lauren intestinal type in 206 (53%) and diffuse or mixed-type in 180 (47%). Median time to recurrence was 12 months and 75% of recurrences occurred within 2 years. There was a significant difference in pattern of initial recurrence between the intestinal and diffuse/mixed cohorts (P < 0.001). For intestinal tumors, distant metastasis was the most common site (54%), followed by locoregional (20%), peritoneal (15%), and multifocal (11%). For diffuse/mixed tumors, peritoneal recurrence was the most common (37%), followed by distant (32%), locoregional (22%), and multifocal (9%). On multivariate analysis, Lauren histologic type was the only significant factor that was associated with both peritoneal recurrence (diffuse, hazard ratio 2.22, confidence interval 1.38-3.94) and distant recurrence (intestinal, hazard ratio 1.888, confidence interval 1.202-2.966). After recurrence, median overall survival was only 8.4 months. In GA patients who recur after resection, patterns of recurrence vary significantly based on Lauren histologic type.

Abstract 4246: Associations of Epstein-Barr virus (EBV)-positive gastric cancer with circulating mediators of inflammation and immune response

Abstract Epstein-Barr virus (EBV) positivity defines one of four major molecular types of gastric cancer in The Cancer Genome Atlas (TCGA). However, viral status is not routinely determined in clinical practice and tumor samples are not generally collected in epidemiologic research. Histologically, EBV-positive gastric cancer is characterized by prominent inflammatory infiltrate. In molecular analyses from TCGA, EBV-positive gastric cancer had significantly higher expression of several chemokines, chemokine receptors and programmed death-ligand 1 (PD-L1) as compared to other molecular types combined. We hypothesized that EBV tumor status may also be reflected in profiles of circulating chemokines and other markers of immune response. We have therefore evaluated pre-treatment EDTA plasma samples of gastric cancer patients from Latvia, including 28 with EBV-positive (as assessed by EBV RNA in situ hybridization) and 34 with EBV-negative tumors, frequency-matched by age, sex, anatomical subsite and Lauren histological type. We measured 92 markers using the Proseek Inflammation Panel I (Olink Proteomics, Uppsala, Sweden). We used logistic regression to model adjusted associations between tertiles of the markers and tumor EBV positivity. P&amp;lt;0.05 was considered statistically significant. Nine markers had undetectable levels in all or almost all samples. Of 83 evaluable markers, 8 were significantly higher in patients with EBV-positive tumors vs. those with EBV-negative tumors, including Chemokine C-C motif ligand (CCL) 20 (odds ratio per tertile [OR]: 3.6; p-trend=0.001), Chemokine C-X-C motif ligand 19 (OR=3.6; p-trend=0.003), PD-L1 (OR=3.4; p-trend=0.004), interleukin (IL) 10 (OR=2.4; p-trend=0.019), CCL19 (OR=2.3; p-trend=0.019), CCL11 (OR=2.2; p-trend=0.026), IL-17A (OR=2.0; p-trend=0.038) and CCL8 (OR=1.9; p-trend=0.049). These eight markers were positively correlated with the 28 pair-wise Spearman correlations ranging from 0.14 - 0.71, of which 24 were statistically significant. A model combining the top three markers, CCL20, CXCL19 and PD-L1, discriminated tumor EBV status with an area under the receiver operating characteristics curve of 0.82. These data indicate that the local alterations of specific chemokines and PDL-1 characterizing EBV-positive gastric tumors are reflected in the systemic circulation. Profiling of these molecules may enable non-invasive diagnosis of EBV-positive gastric cancer and facilitate etiologic and translational studies in large-scale prospective cohorts that lack tumor specimens. Our findings provide additional support for evaluating PD-1 blockade and other immunomodulatory therapies for patients with EBV-positive gastric cancer. Citation Format: M. Constanza Camargo, Armands Sivins, Sergejs Isajevs, Dace Rudzite, Margaret Gulley, G. Johan Offerhaus, Marcis Leja, Charles S. Rabkin. Associations of Epstein-Barr virus (EBV)-positive gastric cancer with circulating mediators of inflammation and immune response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4246. doi:10.1158/1538-7445.AM2017-4246

Alpha-fetoprotein is a significant prognostic factor for gastric cancer: Results from a propensity score matching analysis after curative resection

BackgroundPrognosis of alpha-fetoprotein positive gastric cancer (AFPP-GC) remains elusive so far due to disparities in cohort size and baseline characteristics in previous studies. A propensity score matching (PSM) analysis as well as multivariable model was performed for unbiased evaluation of the outcome in AFPGC. MethodsAmong 3034 gastric cancer patients who underwent curative gastric cancer surgery (R0, M0) at the National Cancer Center, Korea between 2002 and 2007, we identified 97 patients being positive for AFP either by elevation of serum-AFP levels >10 μg/L or by immunohistochemical staining. Due to marked disparities in baseline characteristics and cohort size, propensity-score-matching was performed which matched 87 AFPP-GC patients to the same number of AFP-negative gastric cancer (AFPN-GC) patients. Baseline characteristics were compared using χ2-test. Survival curves were compared using the Kaplan-Meier-method and multivariable regression analysis was performed to evaluate the effect of AFP-positivity while adjusting the effects of confounding variables. ResultsAFPP-GC and AFPN-GC patients revealed marked disparities in patient cohorts. After PSM, groups were balanced for age, sex, tumor size, BMI, tumor location, grade of differentiation, presence of lymphatic vessel infiltration (LVI), Lauren histologic type and stage distribution. In multivariable regression analysis of the PSM-groups, only AFP-positivity and pathologic stage were predictive for overall survival (HR 2.98, CI 95% {1.7–5.1}, p < 0.0001). Five-year-survival rates were significantly worse for AFPP-GC patients (57.9% vs. 76.1%, p = 0.014). Recurrence was significantly more frequent in AFPP-GC patients (p = 0.003). ConclusionAFP can be considered as an independent negative predictor of overall and recurrence-free survival in patients with gastric cancer.

Programmed death-ligand 1 expression in gastric adenocarcinoma is a poor prognostic factor in a high CD8+ tumor infiltrating lymphocytes group.

Gastric adenocarcinoma is one of the most common causes of cancer-related death. In this study, we conducted immunohistochemical studies for PD-L1, PD-1, CTLA-4, and CD8 using tissue microarrays from 464 gastric cancer samples and evaluated the correlations between their expression, clinicopathologic factors, and five-year overall survival. PD-L1 and PD-1 expression was significantly correlated with several adverse prognostic pathologic factors, including higher T-stage, diffuse Lauren histologic type, and lymphatic invasion. Conversely, CTLA-4 expression was correlated with factors of favorable clinical outcomes. A complete case analysis revealed that high PD-L1 and PD-1 expression had an adverse effect on five-year overall survival in univariate analyses. Subgroup analyses wherein patients were divided into two groups according to CD8+ tumor infiltrating lymphocyte levels (high and low) showed that high PD-L1 expression was a significant adverse prognostic factor only in the high CD8+ tumor-infiltrating lymphocytes group. Further research and clinical trials are needed to determine the clinical usefulness of these findings.

Mo1380 Patterns of Initial Recurrence After Curative Resection for Gastric Adenocarcinoma According to Lauren Histologic Type

Mo1380 Patterns of Initial Recurrence After Curative Resection for Gastric Adenocarcinoma According to Lauren Histologic Type

(18)F-FDG PET/CT of advanced gastric carcinoma and association of HER2 expression with standardized uptake value.

Expression of HER2 in gastric carcinoma has direct prognostic and therapeutic implications in patient management. The aim of this study is to determine whether a relationship exists between standardized uptake value (SUV) and expression of HER2 in advanced gastric carcinoma. We analyzed the (18)F-FDG PET/CT results of 109 patients that underwent gastrectomy for advanced gastric carcinoma. The (18)F-FDG PET/CT imaging was requested at the initial staging before surgery. The examinations were evaluated semi-quantitatively, with calculation of maximum standardized uptake values (SUVmax). The clinicopathologic factors, including HER2 overexpression, were determined from tissue obtained from the primary tumor. Metabolic and clincopathologic parameters were correlated using a t-test, one way ANOVA and chi-square test. Immunohistochemically, 26 patients (23.8%) showed HER2 overexpression. This overexpression was significantly associated with high SUV level (P=0.02). The SUV level was significantly correlated with tumor size (P=0.02) and differentiation (P<0.001), and Lauren histologic type (P=0.04). Multivariate analysis showed HER2 overexpression, large tumor size, and differentiation (P=0.022, P=0.002, P<0.001) were significantly correlated with the high level of SUV in advanced gastric carcinoma. No association was found between SUV and T stage and lymph node metastasis. A receiver-operating characteristic curve demonstrated a SUVmax of 3.5 to be the optimal cutoff for predicting HER2 overexpression (sensitivity; 76.9%, specificity; 60.2%). An association exists between high SUV and HER2 overexpression and (18)F-FDG PET/CT could be a useful tool to predict the biological characteristics of gastric carcinoma.

Evaluation of focused sentinel lymph node RT-qPCR screening for micrometastases with the use of the Maruyama computer program

SummaryBackgroundIn this preliminary study, we investigated the sensitivity and specificity of reverse transcriptase (RT)-qPCR lymph node (LN) metastases detection, the accuracy of intraoperative dye navigation, and the incidence of micrometastasis (MM) detection with this protocol, compared to other published studies.MethodsA total of 23 patients were enrolled in the study. The first stained LN was analyzed using RT-qPCR for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) expression, as markers for MM involvement. The Maruyama computer program was used to determine the most likely first metastatic site. These results were compared with the actual staining patterns to evaluate whether the first draining LN was extracted. We analyzed the correlations between MM and tumor characteristics. The incidence of MM detected with the present method was compared to other studies, as markers of the accuracy of the present protocol.ResultsAt 35 threshold cycles, the RT-qPCR had a negative predictive value of 100 % and a positive predictive value of 83.3 %. MM were detected in 4 out of 14 node-negative patients (28.6 %). The extracted sentinel LN coincided in 76.9 % of cases with the most probable first metastatic LN predicted by the Maruyama program. MM were found more frequently in these ‘high-risk’ LNs. Significant differences were found in the Lauren’s histological type distribution and the age distribution among the MM-positive and MM-negative groups.ConclusionOur preliminary results confirm that RT-qPCR is an accurate method of MM detection, that the dye navigation enables the determination of the first draining LN, and that the incidence of MM detection with this focused sentinel LN protocol is comparable to other studies.

Frequência e fatores preditivos relacionados a metástase linfática em câncer gástrico precoce

The standard treatment of gastric cancer still has high morbidity and mortality in western populations. Groups of patients with negligible risk of lymph node metastasis may benefit from less invasive treatments. Data regarding the frequency and predictive factors related to lymphatic metastasis in early gastric cancer are rare. To perform the analysis of frequency and predictive factors related to lymphatic metastasis in patients with early gastric cancer treated in a tertiary center in Brazil. Nine hundred and twenty three patients underwent gastrectomy for gastric adenocarcinoma at the hospital. Of these, 126 had early tumors and were included in the analysis. Clinical and pathological related findings and lymphatic metastasis were evaluated. Lymph node metastases were observed in 7.8% of patients with mucosal tumors and 22.6% of submucosal tumors. The presence of ulceration, Lauren histologic type, tumors larger than 50 mm, submucosal invasion, and presence of lymphatic or vascular invasion were significant factors in univariate analysis. The presence of ulceration, lesions larger than 50 mm, infiltration of the submucosal layer and lymphatic invasion were factors independently related to lymphatic metastasis in multivariate analysis. Ulceration, lesions larger than 50 mm, infiltration of the submucosal layer and lymphatic invasion are independent risk factors related to lymphatic metastasis in early gastric cancer.

Early-stage gastric cancers represented as dysplasia in a previous forceps biopsy: The importance of clinical management

Background and aimsBecause histological examination of gastric lesions by forceps biopsy is of limited accuracy, management on the basis of histological results is occasionally controversial. We examined the characteristics of early gastric cancers that presented as dysplasia resulting from a previous forceps biopsy. Patients and methodsBetween April 2007 and December 2010, 341 gastric adenocarcinoma lesions from 330 patients previously diagnosed histologically via endoscopic submucosal dissection were examined. We retrospectively assessed the characteristics of early gastric cancer according to their initial forceps biopsy results. ResultsIn total, 183 EGCs were diagnosed as dysplasia (53.7%; 89 low-grade and 94 high-grade) and 158 (46.3%) as carcinoma by forceps biopsy before endoscopic submucosal dissection. Significant differences were noted with respect to histologic differentiation of carcinomas, Lauren histologic type, depth of invasion, lymphovascular invasion, and en bloc resection between the dysplastic group and carcinoma group, based on forceps biopsy results. ConclusionA forceps biopsy result is not fully representative of the entire lesion and, thus, endoscopic submucosal dissection should be considered for lesions diagnosed as dysplasia via forceps biopsy in order to avoid the risk of missed carcinomas.

Advanced gastric cancer patients with lymphoid stroma have better survival than those without

Lymphoid stroma is a specific pathologic appearance in gastric cancer. This study aims to compare the clinicopathological characteristics of gastric cancer patients with and without lymphoid stroma. From January 1988 to February 2009, 222 out of 1,959 patients with lymphoid stroma of gastric cancer received gastrectomy at the Department of Surgery, Taipei Veterans General Hospital. Clinicopathological characteristics and survival rates were analyzed and compared among the gastric cancer patients with and without lymphoid stroma. For patients with lymphoid stroma, CD20 expression of B lymphocytes and CD3 expression of T lymphocytes were examined using immunohistochemical stains. Advanced gastric cancer patients with lymphoid stroma had better 5-year survival status than those without lymphoid stroma (44.5% vs. 20.5%, P < 0.001). Univariate and multivariate analyses showed that male gender (P = 0.034), tumor invasion depth (P = 0.001), pathological staging (P = 0.006), and Ming's histological classification (P = 0.041) were significantly correlated with patients with lymphoid stroma. B lymphocytes appeared more in Borrmann type III and IV, diffuse Lauren's histological type, and lymph nodes metastases. Advanced gastric cancer patients with lymphoid stroma had better prognosis than those without lymphoid stroma. B lymphocytes appeared more in aggressive gastric cancer tissues with lymphoid stroma.

HER2 OVEREXPRESSION IN ENDOSCOPIC BIOPSY SAMPLE OF GASTRIC ADENOCARCINOMA BY IMMUNOHISTOCHEMISTRY

Background and aim: HER2 overexpression by immunohistochemistry is a prognostic maker in gastric cancer and helps to select candidates benefitted from targeted therapy with trastuzumab. This study is aimed at the assessing HER2 overexpression and its relationship with endoscopic and histopathological findings of gastric adenocarcinoma. Objectives and methods: Biopsy samples from 92 gastric cancer patients were examined for HER2 status by immunohistochemical staining. Results: 6.5% of tumors were cardia tumors and 93.5% were non-cardia tumors. Using the Lauren classification, 51.1% were intestinal type and 48.9% were diffuse type. Using WHO classification, 54.3% were tubular adenocarcinoma, 7.6% were mucinous adenocarcinoma, 15.2% were signet-ring cell carcinoma, and 22.8% were undifferentiated carcinoma. 32.6% were well-differentiated, 15.2% were moderately-differentiated, and 52.2% were poorly-differentiated carcinoma. HER2 was positive in 20.7% of gastric carcinomas, 50% cardia tumors and 18.6% non-cardia tumors. HER2 positivity among polypoid, fungating, ulcerated, and infiltrative types were 38.5%, 29.7%, 9.1% and 0%, respectively. HER2 overexpression in intestinal type was higher than that in diffuse type (31.9% vs. 8.9%, p = 0.009). HER2 overexpression in tubular adenocarcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, and undifferentiated carcinoma was 28.0%, 14.3%, 7.1% and 14.3%, respectively. HER2 overexpressions were different between differentiation degrees: 30% of well-differentiated tumors, 35.7% moderately-differentiated tumors, and 10.4% of poorly-differentiated tumors (p = 0.037). Conclusions: HER2 overexpression was found in 20.7% of endoscopic biopsy sample of gastric adenocarcinoma and was associated with endoscopic gross characteristic, Lauren histologic type and differentiation degree.

Prevalence of HER2/neu overexpression/amplification in a Hispanic population with gastric adenocarcinoma.

25 Background: In Europe, Asia, and North America, studies have identified that approximately 20% of patients with gastric adenocarcinoma exhibit overexpression of HER2/neu. This group of patients has been shown to benefit from combination therapy with the anti-HER2/neu monoclonal antibody trastuzumab. These findings have not been studied in Hispanics who may possess a distinct gastric cancer genotype. The aim of this study is to determine the rate of HER2/neu positivity in a completely Hispanic population with gastric adenocarcinoma and to analyze the clinical factors associated with HER2/neu. Methods: We conducted a retrospective study in three different hospitals in Monterrey, Mexico. The study population consisted of Hispanic patients with gastric adenocarcinoma who have had a gastric resection and for whom there were adequate amounts of tissue available in paraffin blocks. Tissue was tested for HER2/neu using both Immunohistochemistry (IHC) and the fluorescent in situ hybridization (FISH) techniques. Results: From 2000 to 2010, we initially evaluated 27 gastric cancer tumor samples. Sex distribution was 15 males and 12 females with a mean age of 57±15 (SD) years. Anatomic distribution of tumor was 4% in the cardias, 40% in the body and 56% in the antrum. Lauren's histological type distribution was 52% diffuse and 48% intestinal. Fifty-three percent of the tumors were high grade and nodal positivity was present in 69%. Overexpression of Her-2/neu (IHC ++ and +++) was found in five (17.4%) of the samples, being moderate (++) in two (7.4%) and strong (+++) in three (11%) tumor samples. FISH amplification for the HER2/neu gene was found in two (7.4%) tumors and was only seen in samples with a strong (+++) IHC result. There was no association identified between HER2/neu status with age, gender, degree of differentiation, T stage, or nodal status. Conclusions: In a homogeneous Hispanic population, 17.4% of gastric cancer patients were found to overexpress HER2/neu by IHC. FISH did not identify any additional HER2/neu positive tumors. It is important to consider IHC testing for HER2/neu in Hispanic gastric cancer patients as they could benefit from a chemotherapy regimen containing trastuzumab. No significant financial relationships to disclose.

Prognostic Significance of p53 Protein Expression in Early Gastric Cancer

Mutations of the p53 tumor suppressor gene have been associated with abnormalities in cell cycle regulation, DNA repair and synthesis, apoptosis, and it has been implicated in the prognosis of advanced gastric cancer. The aim of this study was to evaluate the occurrence of p53 gene mutation and its possible prognostic implications in early gastric cancer. In a retrospective study, we studied 80 patients with early gastric cancer treated surgically between 1982 and 2001. Mutation of p53 gene was investigated in surgical gastric specimens by immunohistochemistry, and results were analyzed in relation to gender, age, macroscopic appearance, size and location of tumor, presence of lymph nodes, Lauren's histological type, degree of differentiation, and the 5-year survival. The expression of p53 was more frequent among the intestinal type (p = 0.003), the differentiated (p = 0.007), and the macroscopically elevated tumors (p = 0.038). Nevertheless, the isolated expression of p53 was not associated with the 5-year survival, or with the frequency of lymph node involvement. The degree of differentiation was detected as an independent factor related to the outcome of patients (0.044). Significantly shorter survival time was found in p53-negative compared with p53-positive patients, when considering the degree of differentiation of tumors, as assessed by Cox regression analysis (0.049). The association of p53 with the intestinal type, the degree of differentiation and morphological characteristics, may reflect the involvement of chronic inflammatory process underlying early gastric cancer. In this population sample, the expression of p53 alone has no prognostic value for early gastric cancer. However, the significant difference in p53 expression between subgroups of degree of differentiation of tumors can influence post-operative outcome of patients and may be related to possible distinct etiopathogenic subtypes.

Relationship between Ets-1 expression and angiogenesis, clinicopathological features and survival of patients with gastric carcinoma

To investigate the expression of Ets-1 in gastric carcinoma, para-cancerous tissue and metastatic lymph nodes, and to determine the relationship between Ets-1 expression and clinicopathological features, angiogenesis and survival of patients with gastric carcinoma. Gastric carcinoma tissue microarray was used to determine Ets-1 protein expression by SP immunohistochemical staining in 189 advanced gastric cancer, 54 papacancerous tissues, 41 metastatic lymph nodes and 32 control tissues. The positive rates for Ets-1 expression of the carcinoma, paracancerous and control tissues were 71.4%, 29.6% and 18.8%, respectively, with a significant difference among the three groups (P < 0.01). In the cancer tissues, the positive rate of Ets-1 protein expression was significantly associated with depth of invasion and lymph node metastasis (P < 0.01), but not associated with degree of differentiation, Lauren's histological type, sex, age, and size of tumor (P > 0.05). The positive rates for Ets-1 expression of the 41 gastric cancer and 41 metastatic lymph nodes were significantly different (P < 0.05). In metastatic lymph nodes, the positive rate for Ets-1 expression was higher. The MVD in Ets-1 positive tumors was higher than that in the Ets-1 negative tumors, with a significant difference (P < 0.05). Kaplan-Meier survival analysis showed that the survival time of Ets-1-negative patients was longer than that of Ets-1-positive patients (P < 0.05). Cox regression analysis showed that Ets-1 expression was not an independent prognostic factor of gastric carcinoma. A higher expression of Ets-1 is involved in carcinogenesis, development, invasion, and metastasis of gastric cancer. Ets-1 plays an important role in angiogenesis in gastric cancer. Ets-1 is a useful marker for predicting the outcome for patients with gastric carcinoma, though it is not an independent prognostic indicator.