PS02.092: HER2 EXPRESSION AND GENE AMPLIFICATION CORRELATES WITH BETTER SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 146-147
Author(s):  
Heike Loeser ◽  
Patrick Plum ◽  
Thomas Zander ◽  
Max Kraemer ◽  
Hakan Alakus ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Esophageal Adenocarcinoma ◽  
Gene Amplification ◽  
Growth Pattern ◽  
Prognostic Impact ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Papillary Tumor ◽  
The Impact

Abstract Background Targeting Her2 is highly established in cancers of the upper gastrointestinal tract, since clinical studies showed a survival benefit in Her2-positive gastric cancer. To date there is conflicting data concerning the impact of Her2 expression and gene amplification in esophageal adenocarcinoma (EAC), as most studies do not differ between cancers of the esophagus, gastroesophageal junction and stomach. The aim of this study was to analyze the expression and gene amplification of Her2 in EAC in correlation to clinical and pathological data to verify the prognostic impact. Methods We analyzed 506 patients with esophageal adenocarcinomas that underwent thoraco-abdominal esophagectomy between 1997 and 2013 using a tissue micro array (TMA) for the expression of Her2 by immunohistochemistry (IHC) according to the guidelines. Fluorescence-in-situ-hybridization (FISH) was performed for IHC score 2. The Her2-status was correlated with clinical and pathological data. Results Her2-positivity was found in 11.7% (n = 59) of all EAC (IHC score 3 + or IHC score 2 + with amplification) and demonstrated a significant better overall-survival (OS) in correlation to Her2-negative tumors (median OS 55.0 vs. 22.7 months, P < 0.0001) (Figure below). Overexpression of Her2 was associated with lower tumor stages (pT1/pT2, P = 0.038), absence of lymph node metastases (pN0/pN + , P = 0.030) and was significantly associated with tubular and/or papillary tumor growth pattern (P = 0.029). Conclusion We demonstrated a positive prognostic impact of Her2 expression and gene amplification in a large cohort of EAC, contrary to other solid malignancies including gastric cancer, but according to a large study of EAC from 2012. Her2-positive tumors significantly have a tubular and/or papillary tumor growth pattern, indicating a marker of differentiation in EAC. Disclosure All authors have declared no conflicts of interest.

HER2 Expression in Gastric Cancer and Gastroesophageal Junction Cancer

2020 ◽  
Vol 22 (2) ◽  
pp. 79-82
Author(s):  
Md Azizur Rahman ◽  
Abdullah Md Abu Ayub Ansari ◽  
Kazi Mazharul Islam ◽  
Md Aminur Rahman ◽  
ABM Abdul Matin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Social Impact ◽  
Gastroesophageal Junction ◽  
Treatment Protocol ◽  
Armed Forces ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Cancer Data ◽  
Her2 Positivity

Background: Carcinoma of the stomach is a major cause of cancer mortality worldwide. Due to social impact of gastric carcinoma (GC), there is a need to stratify patients into appropriate screening, surveillance and treatment programs. Although histopathology remains the most reliable and less expensive method, numerous efforts have been made to identify and validate novel biomarkers to accomplish the goals. In recent years, several molecules have been identified and tested for their clinical relevace in GC management. Among the biomarkers with the exception of HER2, none of the biomarkers is currently used in clinical practice, and some of them were described in single studies. Materials and Methods: This prospective type of observational study was performed in the Department of Surgery, Dhaka Medical College Hospital, Dhaka, 6 months from approval of protocol. Total 45 consecutive patients aged 18 years and above without consideration of gender were selected purposefully. Every patient was evaluated by clinical examination, appropriate investigations and after a confirm diagnosis of the tissue from the cancer. All patients have undergone operative intervention and Gastrectomy specimens were subtotal (including cardiac and pylorus), subtotal (including the pylorus), total radical gastrectomy and oesophago-gastrectomy sample. All specimens obtained were immersed in 10% formalin. Samples of whom were sent to the department of pathology, DMCH for histopathology examination. Portion of representative tissue/block was sent to AFIP (Armed Forces Institute of Pathology, Dhaka) for immunohistochemistry to find out the HER2 expression in gastric cancer and gastro-oesophageal cancer. Data was collected in a pre-designed questionnaire by face to face interview. Result and observation: In this study when 45 cases were categorized according to WHO grading system it was observed that majority (30) patients were found in grade II, among them 3(10%) were HER2 positive. But with grade III tumour the HER2 positivity were found more i,e; 37.5% (3/8). Grade- I tumor show HER2 neu expression 28.57% (2/7) and according to location most of the cases with HER2 positive expression was located in the gastro-esophageal junction which is 27.27% (3/11) than gastric carcinoma which is 14.70% (5/34). Conclusion: Most of the patients of gastric and gastrooesophageal junction adenocarcinoma are diagnosed at a very late stage, so they require special attention in treatment protocol, including chemotherapy and immunotherapy for increasing their survivability. The study showed with poorly differentiated (high grade) tumour, the HER2 positivity were found more. Journal of Surgical Sciences (2018) Vol. 22 (2) : 79-82

Survival of patients with HER2-positive gastric cancer with introduction of trastuzumab.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 128-128
Author(s):  
Kohei Shitara ◽  
Yasushi Yatabe ◽  
Masato Sugano ◽  
Keitaro Matsuo ◽  
Chihiro Kondo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Small Sample Size ◽  
Small Sample ◽  
Her2 Status ◽  
First Line ◽  
Her2 Positive ◽  
Line Therapy ◽  
The Impact ◽  
Time Varying Covariates ◽  
Line Chemotherapy

128 Background: ToGA study showed that trastuzumab given in combination with first-line chemotherapy (fluoropyrimidine plus cisplatin) improved the overall survival of HER2-positive patients with advanced gastric cancer (AGC). Meanwhile, the prognostic value of HER2 or the efficacy of trastuzumab in second- or further-line chemotherapy remains controversial. Methods: We retrospectively analyzed 567 patients with AGC who initiated systemic chemotherapy before March 2011. Among them, 287 were evaluated for their HER2 status. HER2 positivity was defined as IHC 3+ or IHC 2+ with amplification by FISH. Treatment outcomes were compared between patients with HER2-positive and HER2-negative AGC. To evaluate the impact of exposure to trastuzumab in any line of chemotherapy, we applied time-varying covariates (TVC) analysis to avoid possible lead-time bias. Results: The median survival time (MST) of HER2-evaluated patients (n=287) tended to be better than that of HER2-non-evaluated patients (n=280, 14.5 vs. 13.2 months; P=0.03). Among the HER2-evaluated patients, 47 (16.3%) were HER2-positive and had longer survival than HER2-negative patients (24.1 vs. 13.4 months; P=0.05). Among the HER2-positive patients, 35 received trastuzumab; 15 patients received it as first-line therapy and 20 received it as second- or further-line therapy. The MST of HER2-positive patients with trastuzumab treatment was significantly longer than that of HER2-positive patients without trastuzumab (26.6 vs. 13.5 months; P=0.015). HER2-negative patients and HER2-positive patients without trastuzumab had similar survival durations. According to multivariate analysis with TVCs, exposure to trastuzumab was independently associated with better prognosis (HR 0.54, P=0.04). Conclusions: Although the retrospective nature and small sample size are major limitations of this study, recent HER2-positive AGC patients showed a better prognosis than HER2-negative patients, especially with the introduction of trastuzumab.

Significance of accurate HER2 testing as a new biomarker in advanced gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 106-106
Author(s):  
Tetsuya Kusumoto ◽  
Hajime Ohtsu ◽  
Hiroyuki Kawano ◽  
Koji Ando ◽  
Satoshi Ida ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Tumor Biology ◽  
Japanese Patients ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Gastroesophageal Junction Cancer ◽  
Her2 Heterogeneity

106 Background: The Trastuzumab for Gastric Cancer (ToGA) study is the first international trial to include Japanese patients with human epidermal growth factor 2 (HER2)-positive advanced or recurrent gastric or gastroesophageal junction cancer, which demonstrated that trastuzumab plus chemotherapy improved overall survival in the overall population (hazard ratio 0.74). HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity and incomplete membrane staining. The aim of the present study was to evaluate the frequency of HER2-positive cases by application of the standard criteria in Japanese patients with advanced gastric cancer (AGC) and to investigate the relationships between HER2 expression and therapeutic responses. Methods: A total of 199 tumor samples were assessed for HER2 expression both by immunohistochemistry (IHC) and HER2 amplification by fluorescence in situ hybridization (FISH). HER2-positive status was defined as IHC2+ and FISH-positive or IHC3+. Objective responses were evaluated in the patients with AGC who were treated with chemotherapy plus trastuzumab or chemotherapy alone based on the HER2 expression status. Results: HER2-positive tumors were identified in 12 patients (5.5%), less than 28.1% in the Japanese subgroup analyses of ToGA study. The positive rates varied with histological type; 14%, 5.3% and 0.95% in the well, moderately and poorly differentiated adenocarcinoma, respectively. Although high concordance between the results of IHC and FISH in all samples was found, IHC2+ samples retested here showed FISH-negative. Of all 10 patients with AGC, 3 patients with HER2-positive tumor were treated with capecitabine/cisplatin plus trastuzumab, and partial response was found in 2 cases; response rates were 67%. Conclusions: Specific consideration and scoring modification are required before embarking on HER2 testing in gastric cancer. Accurate and reliable HER2 testing and scoring will allow appropriate selection of patients eligible for treatment with trastuzumab.

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.

Comparison of HER2 expression by immunohistochemistry and HER2 copy number by digital PCR in tumor tissue during treatment with trastuzumab in the prospective cohort of metastatic HER2-positive gastric cancer patients.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 58-58
Author(s):  
Naoki Takahashi ◽  
Satoru Iwasa ◽  
Tomohiro Matsushima ◽  
Shoichi Miyazawa ◽  
Yosuke Kumekawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Copy Number ◽  
Target Therapy ◽  
Digital Pcr ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Molecular Targeted Drug ◽  
Tumor Tissues ◽  
Number Of Patients ◽  
Pre Treatment

58 Background: Trastuzumab (Tmab) is an active molecular-targeted drug for HER2-positive gastric cancer (GC) patients. HER2 expression is known to change during the treatment of Tmab and HER2 amplification in blood is widely investigated as a new biomarker of the treatment candidate or the monitoring of HER2-target therapy. We evaluated the change of the HER2 expression by immunohistochemistory (IHC) and HER2 copy number by degital PCR during the treatment with Tmab in metastatic HER2-positive GC patients. Methods: Metastatic HER2-positive GC patients treated with Tmab were registered prospectively, and tissues were obtained by biopsy from primary lesions at the following points: (1) pre-treatment, (2) post-treatment, and (3) disease progression during chemotherapy with Tmab. Formalin-fixed paraffin-embedded tissue slides were prepared, and the expression of HER2 expression were scored by IHC and HER2 copy number were evaluated by digital-PCR. Results: Among 20 enrolled patients, HER2 expression was evaluated by IHC in all patients. HER2 copy number was evaluated by digital PCR in 15 patients. A patient was excluded because HER2 expression were not detected by re-evaluation. The median of HER2 copy number of 33 sampling points during the treatment was 6.37 (range: 2.12 - 85.8). The median of HER2 copy number of IHC 3+, IHC 2+, IHC 0-1 were 22.4 (3.37 – 85.8), 2.88 (2.65 – 3.6), 2.37 (2.12 – 3.85), respectively. High level of HER2 copy number was detected in tumor tissues of HER2 IHC 3+ compared with that of IHC≦2+. HER2 expression by IHC was disappeared after treatment of Tmab in 42% of HER2-positive patients. Among these patients, HER2 copy number at pre-treatment were relatively low (2.63 - 3.6). Conclusions: High copy number of HER2 was detected in tumor tissues with HER2 IHC3+ in HER2-positive GC patients during the treatment of Tmab. In addition, low copy number of HER2 in tumor tissues at pre-treatment may be associated with the loss of HER2 expression after treatment of Tmab. Further research by large number of patients to confirm our results is required.

scholarly journals Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Lili Mi ◽  
Lianhui Lei ◽  
Xiaolei Yin ◽  
Ning Li ◽  
Jianfei Shi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Colony Formation ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
The Impact

Abstract Background: Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. Methods: The levels of circ_0000144, miR-623 and G-protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using Western blot. In vivo assays were used to explore the impact of circ_0000144 on tumor growth. Results: Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. Conclusion: Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment.

scholarly journals Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer

2014 ◽  
Vol 18 (4) ◽  
pp. 691-697 ◽  
Author(s):  
Yukinori Kurokawa ◽  
Nariaki Matsuura ◽  
Yutaka Kimura ◽  
Shinichi Adachi ◽  
Junya Fujita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Large Scale ◽  
Prognostic Impact ◽  
Her2 Expression ◽  
Large Scale Study ◽  
Resectable Gastric Cancer
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