scholarly journals Detection of HER2 expression and its structural alterations in gastric cancer tissues infected with cagA+ H. pylori

2020 ◽  
Author(s):  
Akhileshwar Kumar Srivastava ◽  
Divya Singh
Keyword(s):  
Gastric Cancer ◽  
Growth Factor Receptor ◽  
Pcr Amplification ◽  
Receptor Expression ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Gastric Cancer Cells ◽  
H Pylori ◽  
Cancer Tissues

AbstractBackgroundHelicobacter pylori (HP) cagA is the causing agent for development of gastric cancer (GC). H. pylori also involves to trigger the EGFR (epidermal growth factor receptor) expression in gastric cancer cells. However, the prognostic relation of cagA with HER2 status in GC was not well understood.ObjectiveThe main aim of this study was to investigate the link of HER2 expression with CagA+ H. pylori in GC tissues.Materials and MethodsThe study was performed on 85 GC tissues of GC patients. The specific primers of 16S rDNA and cagA for PCR amplification were used. For investigation of HER2 status in GC tissues, immunohistochemistry and PCR amplification were performed. In silico study was performed for the investigation of interactive potential of HER2 with CagA protein.ResultsPCR amplified the 54 (63.52 %) of 85 GC tissues for HP that showed 34 (62.96 %) cagA+ HP. Immunohistochemistry of tissues revealed 57 (67.05 %) diffuse and 28 (32.94 %) intestinal type cancer. Of 85 cases, 21 GC tissues scored (2 + or 3 +) for positive HER2 expression and score (0 or 1 +) of 64 (75.29 %) showed negative. Of 21 HER2 + GC tissue, 15 biopsies had cagA+ HP and 2 were negative. PCR amplified single amplicon in 17 (20 %) CagA+ tissues and 3 (5.55 %) in CagA - HP. The molecular interactions of CagA was also showed its efficiency for HER2 expression.ConclusionThe study concluded that CagA+ HP may induce HER2 overexpression in GC tissues.

scholarly journals Correlations of Human Epithelial Growth Factor Receptor 2 Overexpression with MUC2, MUC5AC, MUC6, p53, and Clinicopathological Characteristics in Gastric Cancer Patients with Curative Resection

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Kwang Kuk Park ◽  
Song I Yang ◽  
Kyung Won Seo ◽  
Ki Young Yoon ◽  
Sang Ho Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Clinicopathological Characteristics ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Poor Prognostic Factor ◽  
P53 Expression ◽  
Gastric Cancer Patients

Background. The purpose of this study was to evaluate the relationships between HER2 overexpression in the tumor and MUC2, MUC5AC, MUC6, and p53 status and clinicopathological characteristics of gastric cancer patients.Methods. This retrospective study included 282 consecutive patients with gastric cancer who underwent surgery at the Kosin University Gospel Hospital between April 2011 and December 2012. All tumor samples were examined for HER2 expression by immunohistochemistry (IHC) and MUC2, MUC5AC, MUC6, and p53 expression by staining. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors.Results. The HER2-positive rate was 18.1%. Although no association was found between HER2 expression and MUC5AC, the expression of MUC2, MUC6, and p53 was significantly correlated with HER2 positivity, respectively (P= 0.004, 0.037, 0.002). Multivariate analysis revealed that HER2 overexpression and nodal status were independent prognostic factors.Conclusions. HER2 overexpression in gastric carcinoma is an independent poor prognostic factor.

scholarly journals Study of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Gastric Carcinoma

2020 ◽  
Vol 7 (47) ◽  
pp. 2747-2751
Author(s):  
Lekshmi Vijayakumaran Nair Lilly ◽  
Geetha Sukumaran
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Gastric Carcinoma ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Intestinal Type ◽  
Treatment Modalities ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Her2 Positive

BACKGROUND Gastric carcinoma is an important cause of cancer related mortality worldwide. Majority of the patients are diagnosed in the advanced stage of the disease. The main treatment modalities are surgery and chemotherapy, but the survival rate of patients with advanced resectable gastric cancer remains poor. For patients with unresectable gastric cancer, chemotherapy remains the treatment of choice. Into this scenario comes the importance of newer targeted therapeutic agents which improve survival rates with acceptable toxicity effects. HER2 is a growth factor implicated in disease initiation and progression, and its expression is associated with a poor prognosis. The aim of this study is detection of HER2 expression in gastric carcinoma and evaluate its relationship with the histopathological characteristics. This would be the stepping stone for patients with tumours that are HER2 positive who could benefit from targeted therapeutical agents like Trastuzumab. METHODS Gastrectomy specimens which were diagnosed as Gastric Carcinoma in the Department of Pathology, Government Medical College, Trivandrum, during a period of two years were included in this study. Routine Haematoxylin and Eosin staining and immunohistochemistry for HER2 were done. RESULTS Thirty eight cases of gastric carcinoma were received during the study period. Intestinal type adenocarcinoma formed the bulk of the tumours (68.42 %), followed by the diffuse type adenocarcinoma (18.42 %). Of the 38 cases, 10 cases showed HER2 positivity. All the positive cases were intestinal type of adenocarcinomas. CONCLUSIONS Our study concluded that 26 % of gastric carcinomas showed positive immunoreaction for HER2 and HER2 overexpression was more in intestinal type adenocarcinomas. HER2 overexpression was also associated with higher stage tumours. There was no association with the patient’s age, gender, location of tumour and tumour differentiation. KEYWORDS Gastric Carcinoma, HER2 expression, Immunohistochemistry, Lauren Classification

Profiling of circulating tumor cells isolated from 105 metastatic gastric cancer patients revealed HER2 overexpression/activation for potential use in clinical setting.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10535-10535 ◽  
Author(s):  
Saswati Hazra ◽  
Jeeyun Lee ◽  
Phillip Sangwook Kim ◽  
Kyoung-Mee Kim ◽  
Limin Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Predictive Marker ◽  
Patient Treatment ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Over Expression

10535 Background: Gastric cancer (GCA) is the second leading cause of cancer mortality in the world. Survival of patients with advanced GCA treated with chemotherapy remains low. New targeted therapies are urgently needed. There is mounting evidence of the role of HER2 overexpression in patients with GCA, and it has been highly correlated to poor outcomes with more aggressive disease. The ability to accurately determine HER2 status by testing circulating tumor cells (CTCs) may improve patient treatment by allowing ongoing assessment of HER2 status during treatment and/or identifying additional patients who could potentially benefit from HER2- targeted therapy. Methods: The Collaborative Enzyme Enhanced Reactive-immunoassay (CEER) was utilized to determine the expression and activation (phosphorylation) levels of HER2 in CTCs isolated from blood specimens obtained from 105 metastatic GCA patients. Results: Utilizing the CEER platform, the levels of HER2 expression and phosphorylation were determined for CTCs isolated from metastatic GCA patients. Evaluable CTCs were found in 33% (35/105) of enrolled patients. Out of 35 patients, 7 patients (20%) have high HER2 over expression, 6 patients (17%) have moderate HER2 expression and 11 patients (31%) have HER2 activation (phospho positive) with no HER2 over-expression. Conclusions: When CTCs were present, the CEER assay identified varying levels of HER2 involvements in 68% of metastatic GCA patients. HER2 positive CTCs could serve as a prognostic and/or predictive marker in patients with advanced GCA and CTC-HER2 profile shifts can be utilized to monitor the treatment efficacy.

scholarly journals Relative Prognostic Value of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Operable Oesophagogastric Cancer

ISRN Surgery ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
David S. Y. Chan ◽  
Fiona Campbell ◽  
Paul Edwards ◽  
Bharat Jasani ◽  
Geraint T. Williams ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
High Specificity ◽  
Endoscopic Biopsy ◽  
Receptor Expression ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Predictive Values

Aims. The aim of this study was to determine the prognostic significance of HER2 receptor expression in operable oesophagogastric adenocarcinoma. Methods. Eighty-five consecutive patients diagnosed with oesophagogastric adenocarcinoma [18 oesophageal (OC), 32 junctional (JC) and 35 gastric (GC)] undergoing potentially curative resection were studied retrospectively. Immunohistochemistry was used to determine HER2 status at endoscopic biopsy and resection specimen. The primary outcome measure was survival. Results. Twenty (24%) patients had HER2 positive tumours which was commoner in JC (14/32, 44% versus 2/18, 11% in OC and 4/35, 11% in GC, P=0.003). The sensitivity, specificity, positive and negative predictive values of HER2 status at endoscopic biopsy were 56%, 93%, 63%, 91% respectively (weighted Kappa=0.504, P<0.0001). Five-year survival in OC HER2 positive negative was 100% and 36% (P=0.167) compared with 14% and 44% (P=0.0726) in JC and 50% and 46% (P=0.942) in GC respectively. Conclusions. Endoscopic biopsy had a high specificity and negative predictive value in determining HER2 status. Patients with JC had a significantly higher rate of HER2 overexpression and this was associated with a nonsignificant poorer survival trend. A larger study is needed to confirm these findings because of the implications for neoadjuvant and adjuvant chemotherapy regimens.

Long Noncoding RNA NEAT1 Promotes Tumorigenesis in H. Pylori Gastric Cancer By Sponging miR-30a To Regulate COX-2/BCL9 Pathway

2021 ◽  
Author(s):  
Xiwu Rao ◽  
Ningning Liu ◽  
Ru Jia ◽  
Yuanyuan Feng ◽  
Zhaozhou Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Gastric Cancer Cells ◽  
Dual Luciferase Assay ◽  
Cox 2 ◽  
H Pylori ◽  
Cancer Tissues ◽  
Lncrna Neat1

Abstract Background: Helicobacter pylori (H. pylori) is a carcinogenic factor for gastric cancer. Our previous study demonstrated that H. pylori decreased the expression of microRNA(miRNA)-30a to promote the tumorigenesis in gastric cancer. However, the upstream regulatory mechanism of miR-30a hasn’t well-elucidated. In this study, we found the long non‑coding RNA (lncRNA) NEAT1 may sponge miR-30a to regulate COX-2/BCL9 pathway. Methods: The expression of NEAT1 was detected in gastric cancer tissues and tumour adjacent tissues by fluorescence in-situ hybridization(FISH) analysis and RT-qPCR. LncRNA-miRNA interaction networks were constructed using the RNAhybird and Starbase v.2.0. and then validated using dual-luciferase assay. The effects of NEAT1 dysregulation on the proliferative, migratory and invasive abilities of H. pylori filtrate infected gastric cancer cells were observed by cell counting kit-8 (CCK-8), colony formation, wound healing test and transwell assays. Western blot and RT-qPCR were performed to detect protein and RNA expression. The Immunohistochemistry(IHC) was carried out to analyze the location and expression of COX-2 and BCL9Results: FISH and RT-qPCR demonstrated that the expression of NEAT1 was up-regulated in gastric cancer tissues, especially in H. pylori gastric cancer tissues, and the expression of NEAT1 is negatively correlated with miR-30a(miR-30a-3p, miR-30a-5p). The proliferation, migration and invasion of H. pylori filtrate infected gastric cancer cells could be largely enhanced by the up-regulation of NEAT1, while the downregulation of NEAT1 decreased these abilities, and miR-30a could reverse the effect of NEAT1 on these abilities. Dual-luciferase assay identified that NEAT1 directly targeted miR-30a(miR-30a-3p, miR-30a-5p).Due to miR-30a(miR-30a-3p, miR-30a-5p) negatively regulated the expression of downstream COX-2 and BCL9, NEAT1 was identified to indirectly upregulate the expression of COX-2 and BCL9.IHC showed that the expression of COX-2 and BCL9 were increased in H. pylori gastric cancer tissues.Conclusion: The study demonstrated that lncRNA NEAT1 may act as a promoter oftumorigenesis in H. pylori gastric cancer, by sponging miR-30a(miR-30a-3p, miR-30a-5p) to regulate COX-2/BCL9 pathway.

scholarly journals Dicer increases the indication for trastuzumab treatment in gastric cancer patients via overexpression of human epidermal growth factor receptor 2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jianhua Wu ◽  
Qun Zhao ◽  
Yue Zhao ◽  
Xiaoyun Zhang ◽  
Yuan Tian ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Antibody Treatment ◽  
Inhibition Effect ◽  
Epidermal Growth

AbstractThe low proportion of gastric cancer (GC) patients with high HER2 expression limits the clinical application of trastuzumab, a humanized epidermal growth factor receptor 2 (HER2) antibody targeting for GC treatment. We found that Dicer was positively correlated with HER2 expression in GC tissue by immunostaining as well as induce HER2 overexpression without increasing invasiveness of GC cell. In addition, both the growth of GC referring to cell proliferation, invasion, migration and apoptosis was inhibited by Dicer overexpression. Moreover, the HER2 overexpression induced by Dicer provided more effective and additive target for trastuzumab to amplify the inhibition effect for GC cells in vitro and in vivo. Furthermore, as assessed in a subsequent experiment, calcitriol induced HER2 overexpression and amplified the inhibition effect of trastuzumab in GC cells referring to proliferation. Our finding demonstrated the calcitriol might increase indication of trastuzumab by inducing HER2 overexpression in GC patients. Dicer would be a potential target that extend the clinical indications of HER2 antibody in patients with low or negative HER2, who were not fit for HER2 antibody treatment before.

scholarly journals HER2 EXPRESSION AS A PROGNOSTIC FACTOR IN METASTATIC GASTRIC CANCER

2016 ◽  
Vol 53 (2) ◽  
pp. 62-67 ◽  
Author(s):  
Pedro Nazareth AGUIAR JUNIOR ◽  
Ricardo ARTIGIANI NETO ◽  
Nora Manoukian FORONES
Keyword(s):  
Gastric Cancer ◽  
Performance Status ◽  
Metastatic Gastric Cancer ◽  
Receptor Expression ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Status Score ◽  
Performance Status Score ◽  
A Performance

ABSTRACT Background - Human epidermal growth factor receptor 2 (EGFR2/HER2/ErbB2) is a transmembrane receptor that stimulates cell proliferation when activated. The correlation of HER2 expression with prognosis has been studied in many cancer types. However, its relationship with survival of patients with metastatic gastric cancer remains unknown. Moreover, there is a lack of information on this issue in a Brazilian population. Objective - To assess the proportion of patients whose tumor cells express HER2 and correlate this with clinical characteristics as well as treatment outcomes. Methods - This was a retrospective study. We included adult patients with metastatic gastric cancer treated at an University Hospital between 2011 and 2015. Patients did not receive anti-HER2 therapy. Receptor expression was evaluated by immunohistochemistry. Survival risk factors were assessed individually with univariate Cox regression, and a P value <0.05 was considered statistically significant. Results - Forty-nine patients were included in this study. However, only 32 had samples assessed for HER2 expression. Five (16%) patients were positive. Among HER2-negative patients, the average age was 54 years, 44% received a treatment protocol with three drugs, 70% had a performance status score 0-1, and 41% had well or moderately differentiated histology. Among HER2-positive patients, the average age was 58 years, 40% received three drugs, 100% had a performance status score 0-1, and 67% had well or moderately differentiated histology. Response rate was evaluated in 28 cases, and there was no difference between the groups (HER2-negative 52% vs. HER2-positive 40%; P=0.62). Survival outcomes were numerically worse among HER2-positive patients. Median progression-free survival was 8.3 months for HER2-positive patients and 10.6 months for HER2-negative patients (HR 1.61, 95% CI: 0.59-4.38); median overall survival was 14.8 months and 16.9 months for HER2-positive and HER2-negative patients, respectively (HR 1.52, 95% CI: 0.50-4.66). Conclusion - HER2 overexpression in metastatic gastric cancer patients may be a predictor of poor prognosis and further validation is warranted.

scholarly journals HER2 Expression, Test Deviations, and Their Impact on Survival in Metastatic Gastric Cancer: Results From the Prospective Multicenter VARIANZ Study

2021 ◽  
pp. JCO.20.02761
Author(s):  
Ivonne Haffner ◽  
Katrin Schierle ◽  
Elba Raimúndez ◽  
Birgitta Geier ◽  
Dieter Maier ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cells ◽  
Growth Factor Receptor ◽  
Metastatic Gastric Cancer ◽  
Her2 Status ◽  
Her2 Expression ◽  
Her2 Amplification ◽  
Her2 Gene ◽  
Amplification Ratio ◽  
Impact On Survival

PURPOSE Trastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2–positive (HER2+) metastatic gastric cancer (mGC). However, not all patients respond and most eventually progress. The multicenter VARIANZ study aimed to investigate the background of response and resistance to trastuzumab in mGC. METHODS Patients receiving medical treatment for mGC were prospectively recruited in 35 German sites and followed for up to 48 months. HER2 status was assessed centrally by immunohistochemistry and chromogenic in situ hybridization. In addition, HER2 gene expression was assessed using qPCR. RESULTS Five hundred forty-eight patients were enrolled, and 77 had HER2+ mGC by central assessment (14.1%). A high deviation rate of 22.7% between central and local test results was seen. Patients who received trastuzumab for centrally confirmed HER2+ mGC (central HER2+/local HER2+) lived significantly longer as compared with patients who received trastuzumab for local HER2+ but central HER2− mGC (20.5 months, n = 60 v 10.9 months, n = 65; hazard ratio, 0.42; 95% CI, 8.2 to 14.4; P < .001). In the centrally confirmed cohort, significantly more tumor cells stained HER2+ than in the unconfirmed cohort, and the HER2 amplification ratio was significantly higher. A minimum of 40% HER2+ tumor cells and a HER2 amplification ratio of ≥ 3.0 were calculated as optimized thresholds for predicting benefit from trastuzumab. CONCLUSION Significant discrepancies in HER2 assessment of mGC were found in tumor specimens with intermediate HER2 expression. Borderline HER2 positivity and heterogeneity of HER2 expression should be considered as resistance factors for HER2-targeting treatment of mGC. HER2 thresholds should be reconsidered. Detailed reports with quantification of HER2 expression and amplification levels may improve selection of patients for HER2-directed treatment.

Sign in / Sign up

Export Citation Format

Share Document