Intestinal-type Gastric Adenocarcinoma Research Articles

Genomic and Pathologic Profiling of Very Well-Differentiated Gastric Adenocarcinoma of Intestinal Type: A Study With Emphasis on Diffuse-Type Transformation.

Very well-differentiated adenocarcinoma of intestinal type is a distinct subtype of gastric cancer characterized by anastomosing glands with a hand-in-hand pattern and low-grade cytologic atypia resembling intestinal metaplasia. This is a slow-growing neoplasm with an indolent clinical course; however, a subset demonstrates transformation into adenocarcinoma with higher-grade histology, typically diffuse-type carcinoma, and behaves aggressively. This study aimed to better characterize the genomic and pathologic features, with a focus on factors associated with diffuse-type transformation. A total of 58 cases with (n=31) and without (n=27) diffuse-type transformation were analyzed for molecular and pathologic features. First, comprehensive deep DNA sequencing was conducted in 18 cases (discovery cohort), followed by a digital droplet polymerase chain reaction of hot spot RHOA mutations in 40 cases (validation cohort). In total, RHOA mutations were the most common alteration (34%), followed by loss of ARID1A (12%), p53 alterations (10%), and CLDN18 :: ARHGAP26/6 fusions (3.4%). FGFR2 amplification was identified in an advanced case with a p53 alteration. Altered p53 expression was recognized only in higher-grade components and was significantly associated with advanced disease ( P =0.0015) and diffuse-type transformation ( P =0.026). A mixed mucin phenotype was also strongly correlated with advanced disease ( P <0.001) and diffuse-type transformation ( P <0.001). Decreased E-cadherin expression was frequently observed (74%) in poorly cohesive components. This study demonstrated that a subset of RHOA -mutant diffuse-type gastric cancers develops through the transformation of very well-differentiated adenocarcinoma of intestinal type. Our observations suggest a mixed mucin phenotype as a risk factor and alterations in p53 and E-cadherin as drivers of diffuse-type transformation.

CEACAM5 and TROP2 define metaplastic and dysplastic transitions in human antral gastric precancerous lesions and tumors.

Mucosal gastric atrophy and intestinal metaplasia (IM) increase the risk for the development of gastric cancer (GC) as they represent a field for development of dysplasia and intestinal-type gastric adenocarcinoma. We have investigated the expression of two dysplasia markers, CEACAM5 and TROP2, in human antral IM and gastric tumors to assess their potential as molecular markers. In the normal antral mucosa, weak CEACAM5 and TROP2 expression was only observed in the foveolar epithelium, while inflamed antrum exhibited increased expression of both markers. Complete IM exhibited weak CEACAM5 expression at the apical surface, but no basolateral TROP2 expression. On the other hand, incomplete IM demonstrated high levels of both CEACAM5 and TROP2 expression. Notably, incomplete IM with dysplastic morphology (dysplastic incomplete IM) exhibited higher levels of CEACAM5 and TROP2 expression compared to incomplete IM without dysplastic features (simple incomplete IM). In addition, dysplastic incomplete IM showed diminished SOX2 and elevated CDX2 expression compared to simple incomplete IM. CEACAM5 and TROP2 positivity in incomplete IM was similar to that of gastric adenomas and GC. Significant association was found between CEACAM5 and TROP2 positivity and histology of GC. These findings support the concept that incomplete IM is more likely associated with GC development. Overall, our study provides evidence of the heterogeneity of gastric IM and the distinct expression profiles of CEACAM5 and TROP2 in dysplastic incomplete IM. Our findings support the potential use of CEACAM5 and TROP2 as molecular markers for identifying individuals with a higher risk of GC development in the context of incomplete IM.

Development of nomograms for predicting the survival of intestinal-type gastric adenocarcinoma patients after surgery

Intestinal-type gastric adenocarcinoma (IGA) is a common phenotype of gastric cancer. Currently, few studies have constructed nomograms that may predict overall (OS) and cancer-specific survival (CSS) probability after surgery. This study is to establish novel nomograms for predicting the survival of IGA patients who received surgery. A total of 1814 IGA patients who received surgery between 2000 and 2018 were selected from Surveillance, Epidemiology, and End Results database and randomly assigned to the training and validating sets at a ratio of 7:3. Then univariate and multivariate cox regression analyses were performed to screen significant indictors for the construction of nomograms. The calibration curve, the area under the receiver operating characteristic (receiver operating characteristic, ROC) curve (the area under curve, AUC), C-index, net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA) curves were applied to assess the performance of the model. The significant outcomes of multivariate analysis revealed that ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, radiotherapy, number of regional nodes examined, number of regional nodes positive) were demonstrated to construct the nomogram for OS and ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, chemotherapy, number of regional nodes examined, number of regional nodes positive) for CSS. The calibration and AUC uncovered their favorable predictive performance. Subsequently, C-index, NRI, IDI and DCA curves further validated the predicative superiority of nomograms over 7th AJCC Stage System. The validated nomogram provides more reliable OS and CSS predictions for postoperative IGA patients with good accuracy, which can help surgeons in treatment decision-making and prognosis evaluation.

Efficacy and potential therapeutic mechanism of Weiwei decoction on Spasmolytic polypeptide-expressing metaplasia in Helicobacter pylori-infected and Atp4a-knockout mice

Ethnopharmacological relevanceSpasmolytic polypeptide-expressing metaplasia (SPEM) is characterized by mucus cell morphologies at the base of gastric glands, which is considered advanced SPEM when accompanied with an increase in transcripts associated with intestinal-type gastric cancer. Weiwei decoction (WWD) was modified from "Si-Jun-Zi Tang," which has been used for thousands of years in China against gastric atrophy and metaplasia. Aim of the studyTo investigate the effects and potential mechanisms of WWD against advanced SPEM. Materials and methodsLiquid chromatography-mass spectrometry was employed to analyze the constituents of WWD. Five-month-infected Helicobacter pylori (H. pylori) Sydney strain 1 C57BL/6J mice and 6-week-old ATPase H+/K+ transporting subunit alpha-knockout mice (Atp4a−/−) were given folic acid (1.95 mg/kg) or WWD (13.65 g/kg, 27.30 g/kg, 54.60 g/kg) by gavage for one month. ResultsWWD demonstrated beneficial effects on gastric mucosal pathology and mucus secretion. In H. pylori-infected mice, WWD effectively reduced the expression of GSII and inhibited the mRNA levels of key markers associated with advanced SPEM, including Clu, Cftr, Wfdc2, Dmbt1, and Gpx2. Similarly, in Atp4a−/− mice, WWD significantly decreased the expressions of GSII and Clusterin, and inhibited the mRNA levels of Wfdc2, Cftr, Dmbt1, and Gpx2. Notably, WWD restored the expression of markers for chief cells (PGC, GIF) and parietal cells (ATP4A), particularly in the medium- and high-dose groups, indicating its potential anti-atrophy effect on H. pylori-infected and Atp4a−/− mice. WWD administration resulted in a decline in TFF2 expression to baseline levels, suggesting that the mucous protection mediated by TFF2 was unaffected. Furthermore, the infiltration of CD163+F4/80+ M2 macrophages in the gastric mucosa of H. pylori-infected mice was reduced after WWD treatment, indicating a potential modulatory role of WWD on M2 macrophages. ConclusionWWD exerted protective effects against SPEM in H. pylori-infected and Atp4a−/− mice. The optimal doses of WWD were found to be medium doses in H. pylori-infected mice and high doses in Atp4a−/− mice. These effects include inhibition of transcripts associated with intestinal-type gastric adenocarcinoma, restoration of ATP4A and PGC expression, and reduction of M2 macrophage infiltration. These findings provide valuable insights into the therapeutic effects of WWD on advanced SPEM and highlight its potential as a treatment option.

Phase I/II study of nab-paclitaxel combined with S-1 as adjuvant chemotherapy in diffuse type of stage III gastric or gastroesophageal junction adenocarcinoma.

e16064 Background: Diffuse type (Lauren's classification) of gastric adenocarcinoma (GAC) or gastroesophageal junction adenocarcinoma (GEJ) has a poorer prognosis than intestinal type of GAC or GEJ. Studies have shown that nab-paclitaxel combined with S-1 has a synergistic anti-tumor effect on advanced gastric cancer. We designed this trial to evaluate the efficacy and safety of nab-paclitaxel plus S-1 as adjuvant chemotherapy in diffuse type of stage III GAC or GEJ. Methods: This study was a multi-center, open-label, phase I/II study. The results of the phase I dose escalation study have already been reported, and the recommended phase II dose (RP2D) of nab-paclitaxel is 260mg/m2. Patients with stage III diffuse type GAC or GEJ after D2 dissection and achieved R0 resection were included in this study. S-1 monotherapy was used as adjuvant therapy in the first cycle. If absence of grade3/4 treatment-related adverse events (AEs) of S-1 monotherapy, nab-paclitaxel (260mg/m2, d1, q3w) and S-1 [body surface area (BSA) &lt;1.25 m2, 80mg/d; BSA 1.25–1.5 m2, 100mg/d; BSA &gt;1.5 m2, 120mg/d; d1-14, q3w] were administered for 6 cycles. Then patients still received S-1 monotherapy for 8 cycles. In phase II study, the primary endpoint was 1-year disease free survival (DFS) rate, and the secondary endpoints were 3-year DFS rate and safety. Results: From January 2021 to February 2023, a total of 42 patients were enrolled in this analysis (3 patients in nab-paclitaxel 260mg/m2 dose group in phase I and 39 patients in phase II). The median age (range) was 53 (29~69) years, 18 patients (42.86%) were stage IIIA, 10 patients (23.81%) were stage IIIB and 14 patients (33.33%) were stage IIIC. The median follow-up time was 13.26 months. As of January 2023, 12 patients experienced recurrence. The 1-year-DFS rate was 74.07%, median DFS and 3-year-DFS rate were not reached. The incidence of adverse effects (AEs) was 78.57% (33/42), and the rate of grade 3-4 AEs was 42.86% (18/42). The most common AEs were neutropenia and leukopenia. In addition, we performed next generation sequencing (NGS) for 5 relapsed patients, and 5 non-relapsed patients who were matched to the relapsed patients. The results showed that the mutant rates of tumor supressor gene CDH1, ARID1A, KMT2D, and TP53 in non-relapsed patients were higher than that in relapsed patients. The positive rate of ctDNA were 60% in relapsed patients, but no ctDNA was detected in non-relapsed patients. Conclusions: Adjuvant chemotherapy with nab-paclitaxel and S-1 followed by S-1 monotherapy exhibited promising clinical efficacy, with acceptable tolerability. This study deserves further investigation and follow up for diffuse type of GAC or GEJ. Clinical trial information: NCT03977220 .

Prediction models for the survival in patients with intestinal-type gastric adenocarcinoma: a retrospective cohort study based on the SEER database

ObjectiveTo explore the influencing factors of survival in intestinal-type gastric adenocarcinoma (IGA) and set up prediction model for the prediction of survival of patients diagnosed with IGA.DesignA retrospective cohort study.Setting...

E-cadherin Immunoexpression Patterns in Gastric Carcinoma Histological Subtypes: A Hospital-based Descriptive Study

Introduction: Gastric carcinoma is the second common Gastrointestinal (GIT) malignancy. Based on Global Cancer Observatory (GLOBOCAN) 2020 data, it is the 5th most common neoplasm and the 4th most common cause of death. Epithelialcadherin (E-cadherin) is a transmembrane glycoprotein which plays a crucial role in maintaining cell-cell adhesion. Loss of E-cadherin contributes to enhanced invasion and metastasis in human cancers. Aim: To study E-cadherin immunohistochemical expression in tumour cells and its association with gastric carcinoma histotypes. Materials and Methods: It is a hospital-based descriptive study conducted at Department of Pathology, Osmania General Hospital, Hyderabad, Telangana, India from January 2010 to December 2012 as it was my dissertation. Routine histopathology and immunohistochemistry for E-cadherin were done on the sections. E-cadherin immunohistochemical staining and expression in tumour cells were evaluated according to the study by Jawhari A et al., Scores (0-3) were applied: 0-No staining; 1-Only cytoplasmic staining; 2-Cytoplasmic and membranous staining in the same case, 3-Normal membranous immunoexpression. Staining was evaluated based on absence of membranous expression scores (0 and 1) versus the presence of membranous expression (scores 2 and 3). Statistical analysis of the data was done by Chi-square test using Epi Info software. Results: Total 70 cases were studied, of which 48 were gastric biopsies and 22 were gastrectomies. Gastric adenocarcinomas were classified as intestinal 40 cases (57.14%) and diffuse 30 cases (42.85%) according to Lauren’s classification. Membranous staining of E-cadherin was seen in 34/40 cases (85%) of intestinal gastric cancer and 9/30 cases (30%) of diffuse intestinal cancer whereas non membranous or absent E-cadherin was seen in 6/40 cases (15%) of intestinal gastric cancer and 21/30 cases (70%) of diffuse gastric cancer. In this study, significant association was found between membranous E-cadherin expression (score 2 or 3) and intestinal histotype and absence of membranous expression (scores 0 or 1) and the diffuse histotype of gastric cancer. Conclusion: Normal gastric mucosa shows strong membranous E-cadherin positivity. There is a change in the pattern of E-cadherin expression from membranous in intestinal type gastric adenocarcinoma to non membranous expression of E-cadherin in diffuse type of gastric carcinoma.

Expression of PD-1 in Tumor Cells is Associated with Shorter Survival in Non-metastatic Intestinal-type Gastric Adenocarcinoma.

There is an urgent need to discover novel prognostic biomarkers and treatment strategies for gastric cancer (GC) patients. Several immune-related markers have been proposed as prognostic tools and immunotherapeutic targets to manage diseases. In this regard, we evaluated the expression pattern and prognostic significance of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), CD45RO+ tumor-infiltrating lymphocytes (TILs), and DNA mismatch repair (MMR) proteins (MLH1, MSH2, PMS2, and MSH6) in non-metastatic intestinal-type gastric adenocarcinoma. Samples and data from 70 GC patients were collected. Immunohistochemistry staining was used to detect the markers. We then evaluated the prognosis significance of each marker and their intercorrelation. Cytoplasmic PD-1 expressed by tumor cells was significantly associated with poorer survival. However, multivariate analysis indicated stronger prognostic values for TNM stage, tumor location, and extracellular mucin. A significant positive association was found between CD45ROhigh TILs and PD-1 expression on tumor-infiltrating cells (TICs). All GC patients with deficient MMR (d‑MMR) had a higher number of CD45RO+ TILs and were associated with PD-1+ TICs and PD‑L1+ tumor cells (TCs). However, the difference was not statistically significant. Despite the association of PD‑1 overexpression on TCs with shorter overall survival, histopathological factors, includingtumor location, TNM stage, and extracellular mucin, remain the most decisive prognostic factors in non-metastatic intestinal-type gastric adenocarcinoma. Additionally, our data support a prognostic role for d-MMR and CD45RO, but not PD-1 and PD-L1 expression on TICs.

Descriptive Study of Tumor Immune Microenvironment and Epstein-Barr Virus Infection in Gastric Adenocarcinoma

Introduction. The Cauca region, in Colombia, has a high incidence of gastric cancer and there are few studies describing tumor microenvironment in gastric cancer samples obtained from this geographic region. Aim. The aim of this study was to describe the infiltration of CD3+, CD8+ T cells, the expression of programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1), and Epstein-Barr virus infection in biopsies from Cauca patients with advanced intestinal-type gastric adenocarcinoma. Methodology. This is a descriptive cross-sectional study of 24 gastrectomy samples out of 48 samples analyzed. Expression of CD3, CD8, PD-1, and PD-L1 was analyzed using immunohistochemistry, and infection by Epstein-Barr virus was analyzed by Epstein-Barr virus-encoded small RNA in-situ hybridization (EBER-ISH) in gastric tissue samples on formalin-fixed, paraffin-embedded. Finally, the immunoscore and the Combined Positive Score were calculated. Results. ITGA samples were 21.8% ± 13.6% and 14.8% ± 14.8% CD3 + and CD8 + positive respectively, 100% had low PD-1 expression, CPS score for PDL-1, 91.7% had &lt;1 and 8.3% had &gt;1. In EBER-ISH, 20.8% were positive, and in immunoscore, 16.7% had a score &gt; 25%. Conclusion. This paper reports advanced ITGA cases with an atypical tumor microenvironment, compared to previously reported data. It is important to consider that the tumor microenvironment in gastric cancer is heterogeneous, which makes the analysis of microsatellite instability in this type of sample relevant.

Further prognostic stratification of intestinal type of gastric adenocarcinoma by CDX2 expression pattern

Gastric cancer is one of the most deadly malignancies worldwide. It is routinely divided into 2 common histologic subtypes by the Lauren classification, intestinal type and diffuse type. In recent years, the intestinal type of gastric cancer has been found to represent a heterogeneous disease with divergent prognosis. Our objective was to investigate the CDX2/CK7 immunohistochemical pattern and its role in further stratifying this type of gastric cancer. Gastrectomy cases with a diagnosis of the intestinal type of gastric adenocarcinoma from a single large institution between 2008 and 2022 were collected. Forty-four cases with available blocks and enough tumor tissue were included in this study. Four different immunohistochemical patterns were identified: CDX2+/CK7+ (40.9%), CDX2-/CK7+ (34.1%), CDX2+/CK7- (18.2%), and CDX2-/CK7- (6.8%). Compared to CDX2-negative cases, CDX2-positive ones are more likely to present better prognostic histopathological features including early stage, less perineural and lymphovascular invasion, and lower nodal metastasis. In addition, CDX2 expression was associated with specific molecular features like HER2 overexpression and genetic alterations of receptor tyrosine kinase (TRK) genes including EGFR, ERBB2, ERBB3, DDR2, and MET. In conclusion, according to the CDX2 expression pattern, the intestinal type of gastric cancer could be further divided into 2 subgroups, which have different histopathological and molecular features and different prognosis.

ABCL-260 Coexistence of Non-Hodgkin Lymphoma and Rectal and Stomach Adenocarcinomas: A Case Report

The exceptional case described by us involves several malignant neoplasms in one person at the same time and the patient's death from COVID-19 complications. Case Presentation: A 74-year-old woman had suffered from marginal zone B-cell lymphoma since 2007. She was under observation until 2013 when there was a progression of the disease. She received 6 non-complete courses of chemotherapy by the R-CVP program. The 6th course was completed in February 2014 because of neuropathy. As a result, clinical hematological remission was registered. Until 2018, the situation was stable and dynamic control continued. In 2018-2019, a tendency toward lower hemoglobin was observed, CT revealed a conglomerate up to 11 cm in the abdomen, a biopsy of the axillary lymph nodes was performed, and Grade I follicular lymphoma was found. The size of the conglomerate did not change during the year and iron deficiency anemia was expressed in the blood test, though other test indicators were within the norm. Significant weight loss of 10 kg was observed in 1.5 years. In February 2019, a colonoscopy was performed, revealing a tumor, and in March 2019, a hemicolectomy was performed. Immunohistochemical examination of the removed tumor confirmed invasive mucinous adenocarcinoma Low-Grade p73pN1b (2/12) pMxL1V0Pn0Rx. The patient continued with permanent diarrhea and anemia. After two years, in May 2021, the patient was admitted for chronic muscular pain. During hospitalization, an episode of melena occurred, following which she underwent both colonoscopy and gastroscopy; the latter disclosed an approximately 1.2-cm lesion in the greater curvature of the stomach. The patient underwent trepan biopsy, which revealed intestinal-type gastric adenocarcinoma. The patient received 3 courses of rituximab monotherapy and was discharged before surgery. However, COVID-19 changed the plans of the doctors and the patient died from its complications in the intensive care unit. Conclusions: The synchronous occurrence of non-Hodgkin lymphoma and rectal and stomach adenocarcinoma is rare but possible. Doctors must be alert to its existence. Treatment depends on the tumor stage of the adenocarcinomas but also the lymphoma and its grade, and any therapeutic decision should only be made in a multidisciplinary meeting.

Clinical and pathologic characteristics of gastric adenocarcinoma associated with Epstein-Barr virus in a region with a high incidence of gastric cancer in Colombia

Introduction and aimsEpstein-Barr virus (EBV) infection is an etiologic factor in EBV-associated gastric carcinoma (EBVaGC). The aim of our study was to describe the clinical and histopathologic characteristics of EBV infection in intestinal-type gastric adenocarcinoma samples. Material and methodsOf 180 paraffin-embedded gastrectomy samples, 28 were studied. Chromogenic in situ hybridization was performed to detect EBV. Sociodemographic and histopathologic data were obtained from the patients’ clinical histories. ResultsA total of 21.4% of the samples were positive for EBV. The predominant morphologic characteristic was the lace pattern, with dense inflammatory infiltration. Fifty percent of the EBVaGC+ patients were men, and the median age of the positive patients was 59 years (range: 50–75); 77.2% of the EBVaGC− patients were men, and the median age of the negative patients was 66 years (range: 34–89). Helicobacter pylori infection was associated with 10.7% of the EBVaGC+ patients and 53.6% of the EBVaGC− patients. In the EBVaGC+ patients, the cardia was the most frequent tumor location (17.9%), 7.1% had histologic grades 2 and 3, and 17.9% presented with Borrmann classification type III. In the EBVaGC− patients, the cardia and fundus were the most frequent tumor locations (71.4%), 35.7% had histologic grade 2, and 39.3% and 21.4% presented with Borrmann classification type III and IV, respectively. ConclusionsThe present study describes the clinical and histopathologic characteristics associated with EBVaGC positivity. Those data may aid in the selection of cases that are candidates for analysis through molecular methods aimed at identifying EBV infection in intestinal-type gastric adenocarcinoma.

Prognostic Significance of Tumour Budding and Desmoplastic Reaction in Intestinal-Type Gastric Adenocarcinoma.

Objective. Tumour budding and desmoplastic reactions in peritumoural stroma are features of the tumour microenvironment that are associated with colorectal cancer prognosis but have not been as thoroughly examined in gastric cancer. We aimed to further characterize the prognostic role of tumour budding and desmoplastic reaction in gastric adenocarcinoma with intestinal differentiation. Methods. 76 curative gastrectomy specimens were identified, excluding post-neoadjuvant cases or cases with >50% diffuse-type histology. Tumour budding was defined and graded according to the International Tumor Budding Consensus Conference recommendations and desmoplastic reaction was classified as described by Ueno et al 2017. Tumour budding and desmoplastic reaction were analyzed for associations with pathologic features and clinical outcomes. Results. Tumour budding was associated with pT (P < .001), pN (P < .004), overall stage (P < .001), LVI (P < .001) and PNI (P = .002). Desmoplastic reaction was associated with pT (P < .001), pN (P = .005), overall stage (P = .031) and PNI (P < .001), but not LVI. Survival analysis showed decreased overall survival (OS) and recurrence-free survival (RFS) for intermediate and high grade tumour budding (P = .031, .014 respectively). Immature stroma was significantly associated with RFS but not OS. Neither tumour budding nor desmoplastic reaction were independent predictors of OS or RFS on multivariate analysis in this cohort. Conclusion. Tumour budding and desmoplastic reaction were associated with known pathologic risk factors. Prognostically, tumour budding was associated with OS and RFS while desmoplastic reaction was associated with RFS only. Our data suggest that tumour budding and desmoplastic reaction have prognostic value in intestinal-type gastric adenocarcinoma.

Características clínico-patológicas del adenocarcinoma gástrico asociado al virus de Epstein-Barr en una región de alta incidencia de cáncer gástrico en Colombia

Introduction and aimsEpstein-Barr virus (EBV) infection is an etiologic factor in EBV-associated gastric carcinoma (EBVaGC). The aim of our study was to describe the clinical and histopathologic characteristics of EBV infection in intestinal-type gastric adenocarcinoma samples. Material and methodsOf 180 paraffin-embedded gastrectomy samples, 28 were studied. Chromogenic in situ hybridization was performed to detect EBV. Sociodemographic and histopathologic data were obtained from the patients’ clinical histories. ResultsA total of 21.4% of the samples were positive for EBV. The predominant morphologic characteristic was the lace pattern, with dense inflammatory infiltration. Fifty percent of the EBVaGC + patients were men, and the median age of the positive patients was 59 years (range: 50-75); 77.2% of the EBVaGC– patients were men, and the median age of the negative patients was 66 years (range: 34-89). Helicobacter pylori infection was associated with 10.7% of the EBVaGC + patients and 53.6% of the EBVaGC– patients. In the EBVaGC + patients, the cardia was the most frequent tumor location (17.9%), 7.1% had histologic grades 2 and 3, and 17.9% presented with Borrmann classification type III. In the EBVaGC– patients, the cardia and fundus were the most frequent tumor locations (71.4%), 35.7% had histologic grade 2, and 39.3% and 21.4% presented with Borrmann classification type III and IV, respectively. ConclusionsThe present study describes the clinical and histopathologic characteristics associated with EBVaGC positivity. Those data may aid in the selection of cases that are candidates for analysis through molecular methods aimed at identifying EBV infection in intestinal-type gastric adenocarcinoma.

Evaluation of Human Epidermal Growth Factor Receptor 2 Expression in Gastric and Gastroesophageal Cancers in Tanzania.

The incidence of human epidermal growth factor receptor 2 (HER2) positivity in gastric cancers differs widely across various populations and is unknown in many low-resource settings. To evaluate the rates of HER2 positivity in gastric and gastroesophageal adenocarcinoma at a national referral hospital in East Africa. We also assessed the association between HER2 overexpression and patient clinicopathologic characteristics. A retrospective review of cases diagnosed as either gastric or gastroesophageal adenocarcinoma between 2013 and 2017 was performed at Muhimbili National Hospital in Dar es Salaam, Tanzania. Of 1205 specimens meeting inclusion criteria, stratified random sampling was conducted to select 150 cases for HER2 immunohistochemistry and clinicopathologic analysis. The median age of patients was 56.5 years, with 65.3% (98 of 150) of the cohort composed of male patients, and 34.7% (52 of 150) of female patients. HER2 overexpression was identified in 6.0% (9 of 150) of cases. Approximately half of the tumors (51.3%; 77 of 150) were intestinal-type gastric adenocarcinoma, and 36.0% (54 of 150) were moderately differentiated. Intestinal-type (P = .01) and well-differentiated tumors (P = .001) were associated with HER2 overexpression. HER2 overexpression was primarily seen in intestinal-type and well-differentiated tumors. Therefore, prioritizing HER2 testing for patients with intestinal-type, well-differentiated, or moderately differentiated gastric and gastroesophageal adenocarcinomas may be appropriate in Tanzania in efforts to allocate testing for patients who are most likely to benefit from trastuzumab therapy.

L22 ribosomal protein is involved in dynamin-related protein 1-mediated gastric carcinoma progression

ABSTRACT Mitochondrial fission depends on dynamin-related protein 1 (Drp1) guanosine triphosphatase activity. Although there is some association between Drp1 and gastric cancer, the detailed mechanism remains largely unknown. In this study, the elevation of Drp1 was observed in human gastric carcinoma specimens including gastric mixed adenocarcinoma tissues, gastric intestinal-type adenocarcinoma tissues, and human gastric cancer cells compared to normal control, but not in diffuse gastric adenocarcinoma tissues. Gastric cancer patients with high Drp1 harbored advanced pathological stages and poor progression-free survival probability compared to those with low Drp1. Mdivi-1-mediated inactivation of Drp1 robustly inhibited cell viability and tumor growth but conversely induced cell apoptotic events in vitro and in vivo. Based on the Encyclopedia of RNA Interactomes Starbase, L22 ribosomal protein (RPL22) was recognized as the potential downstream oncogene of Drp1. Clinically, the significant correlation of Drp1 and RPL22 was also verified. Mechanistically, Drp1 inactivation did not affect the accumulation of RPL22 in gastric carcinoma. However, the intracellular distribution of RPL22 had an endonuclear location in Drp1-inactivated tumors. Of note, Drp1 inactivation notably reduced the expression of cytoplasmic RPL22 and increased its nuclear level in gastric cancer cells. Collectively, Drp1 had high levels in human gastric carcinoma specimens and could serve as a potential diagnostic and prognostic biomarker in gastric carcinoma. The Drp1 inactivation-mediated anti-proliferative and pro-apoptosis effects on gastric cancer were possibly associated with nuclear import of RPL22. This knowledge may provide new therapeutic tools for treating gastric carcinoma via targeting mitochondria-related ribosome pathway.

OLGA- and OLGIM-Based Staging in the Patients with Gastritis and Endoscopy Indications.

Gastric cancer is one of the most common cancers with high mortality. In Iran, the high-risk regions include Northern and Northwestern parts. The aim of this study was to assess the operative link on gastritis assessment- and operative link on gastric intestinal metaplasia-based staging in patients with upper gastrointestinal symptoms. Totally, 345 patients underwent upper gastrointestinal endoscopy. Also, the status of Helicobacter pylori infection was evaluated using rapid urease test and histological method. Moreover, histological changes were assessed using the Update Sydney System. The operative link on gastritis assessment- and operative link on gastric intestinal metaplasia-based stages of 0-II were considered as low-risk stages and stages III and IV were considered as high-risk stages. Most of the patients were lower than 60 years (245 patients, 71%), and 71.9% of our patients had H. pylori infection. The frequency of atrophic gastritis and intestinal metaplasia was 44.9% and 25.2%, respectively (P < .001). Eleven patients (73.7%) with gastric adenocarcinoma had a low risk and 2 patients with low-grade dysplasia had a high risk of operative link on gastritis assessment and operative link on gastric intestinal metaplasia. Almost, 62.5% of gastric cancer patients with an intestinal type of gastric adenocarcinoma were at low-risk stages. Although high stages of operative link on gastritis assessment and operative link on gastric intestinal metaplasia need further follow-up, lower stages of atrophy or intestinal metaplasia also require follow-up. Furthermore, operative link on gastritis assessment method in detecting a greater number of patients who need follow-up is more successful and profitable.

Resection of Gastric Cancer Liver Metastases: Literature Review and Case Report

Introduction: The treatment of gastric cancer has undergone changes in recent years, significantly impacting the morbidity and mortality caused by the disease. However, the treatment of metastatic disease remains a challenge. Whether in the intestinal or Lauren's diffuse tumor, the presence of liver metastases in gastric cancer is considered to be an unfavorable prognosis, given the possibility of the existence of other occult metastases at the time of this diagnosis. Given the changes in the panorama of this disease, it is necessary to review the proposed treatment, considering the possibility of oncological benefit from liver metastasectomy and which patients would benefit from this therapy. Clinical case: FAM, female, 65 years old, diagnosed with Lauren's intestinal-type gastric adenocarcinoma submitted to subtotal gastrectomy with D2 lymphadenectomy. Clinical staging IIIB (T4N2M0), referred for adjuvant chemotherapy protocol. At the time no synchronous distant metastases was identified. One year later PET-CT showed a liver nodule at the right lobe and peri-portal nodule. Submitted to right hepatectomy + peri-portal lymphadenectomy. Anatomopathological exame confirmed gastric adenocarcinoma. Conclusion: Review of published studies in the literature showed that patients who would benefit from this therapy would be those with 1-3 metastatic liver lesions, up to 5 cm in length in the largest one, without serosa invasion in the primary lesion and whose lymph node involvement was ≤ N1 . Overall patient survival was increased from 9.5-14.1 months to 31.1-40.8 months in these groups. We therefore conclude that there is benefit in resection of liver metastases in selected cases of gastric cancer.

Grading of tumor budding in intestinal-type early gastric adenocarcinoma and its role in assessing the risk of lymph node metastasis

Objective: To investigate the role of tumor budding (TB) in predicting lymph node metastasis of intestinal-type early gastric adenocarcinoma, and to determine the optimal cutoff value of TB number. Methods: A total of 202 patients with intestinal-type early gastric adenocarcinoma, who underwent surgical operation at the Affiliated Wuxi People's Hospital of Nanjing Medical University, Jiangsu, China from 2008 to 2018 were included. According to the International Tumor Budding Consensus Conference (ITBCC) criteria, the number of TB for each case was assessed. The receiver operating characteristic (ROC) curve was employed to determine the optimal cutoff value of TB number for predicting lymph node metastasis, and multivariate logistic regression was used to analyze whether a high TB number was an independent risk factor for lymph node metastasis. In addition, in the patients, who met the indications for endoscopic resection and developed lymph node metastasis, the association of a high number of TB with lymph node metastasis was examined. Results: TBs were observed in 63.4% (128/202) of intestinal-type early gastric adenocarcinomas. Using ROC curve, 4 TBs was found as the optimal cutoff value to predict lymph node metastasis (area under the curve 0.767; sensitivity 0.657; specificity 0.780). Therefore, the 202 cases were divided into two groups: the high-budding (≥4 TBs) group (n=60) and the low-budding (<4 TBs) group (n=142). The high-budding group exhibited a higher rate of lymph node metastasis than that of the low-budding group (41.7% vs 9.1%, P<0.01), and ≥4 TBs was associated with deeper invasion and lymph vessel invasion (P<0.01). The multivariate regression model showed that ≥4 TBs was an independent risk factor for lymph node metastasis (Hazard ratio=8.760, 95%CI 2.648-28.987; P<0.01). Meanwhile, 4 TBs as the cutoff value could better predict lymph node metastasis than the cutoff value advised by the ITBCC. In addition, 3 cases were found to have developed lymph node metastasis even that they met the expanded indications for endoscopic resection, and 2 of these 3 cases exhibited a higher TB number (≥4 TBs). Conclusions: More than 4 TBs are a useful indicator for predicting lymph node metastasis in intestinal-type early gastric adenocarcinoma. It may be used to as an endoscopic resection criterion for patients with a high risk of lymph node metastasis.

Diagnostic and therapeutic potencies of miR-18a-5p in mixed-type gastric adenocarcinoma.

Mixed‐type gastric adenocarcinoma (by Lauren Classification) has poor clinical outcomes with few targeted treatment options. The primary objective of this study was to find the prognostic factors, accurate treatment approaches, and effective postoperative adjuvant therapy strategies for patients with mixed‐type gastric adenocarcinoma (GA). A microRNA sequencing data set and the corresponding clinical parameters of patients with gastric cancer were obtained from The Cancer Genome Atlas. Differentially expressed microRNAs (DEMs) of diffuse‐ and intestinal‐type GA were, respectively, determined. Kaplan–Meier and log‐rank tests were subsequently carried out to evaluate the prognostic relevance of each DEM. To study the common factors between diffuse‐ and intestinal‐type GA, a pathway enrichment analysis was performed on the target genes of identified DEMs using the PANTHER database. After data preprocessing, we analyzed a total of 230 samples from 210 patients with GA. Eighty‐six DEMs in diffuse‐type GA samples and 59 DEMs in intestinal‐type GA samples were, respectively, identified (p 2.0). The Kaplan–Meier survival method further screened out six prognosis‐related DEMs for diffuse‐type GA and seven prognosis‐related DEMs for intestinal‐type GA (p < 0.05). MiR‐18a‐5p was found to be the only common prognosis‐related DEM between diffuse‐ and intestinal‐type GA. The common signaling pathways further revealed that target genes of miR‐18a‐5p are involved in mixed‐type GA progression. This study suggests that miR‐18a‐5p acts as a potential target for treatment, and common signal pathways provide a rich basis to seek reliable and effective molecular targets for the diagnosis, clinical treatment, and postoperative adjuvant therapy strategy of mixed‐type GA.