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

A comparison of immunohistochemistry (IHC) and dual-color silver in situ hybridization (SISH) with a novel method combining both gene and protein platforms on a unique slide for testing the HER2 in gastric carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4100-4100
Author(s):  
Dominique Werner ◽  
Achim Battmann ◽  
Kristina Steinmetz ◽  
Tobin Jones ◽  
Michele Martinez ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Adequate Treatment ◽  
Feasible Alternative ◽  
Staining Methods ◽  
Novel Method ◽  
Good Concordance ◽  
First Time ◽  
Her2 Positivity

4100 Background: Amplification and/or protein overexpression of HER2 in gastric cancer is a prerequisite to establish an adequate treatment strategy. The European standard defined HER2 positivity by IHC as first evaluation assay followed by ISH in 2+ cases. Gastric tumors are heterogeneous and separate evaluations lead to uncertainties and in localizing distinct clones and are time consuming. The aim of this study was to evaluate the feasibility of gene-protein platform in comparison to single staining methods. Methods: IHC plus SISH and gene-protein platform (IHC/SISH, protein/gene) method for HER2 were performed in randomly collected 100 cases of gastric carcinoma. Results of IHC and SISH were compared with IHC/SISH staining. Rüschoff criteria were applied. Tumors were HER2 positive when expression 3+ or 2+ plus gene amplification (EU-Norm) was found. In Second definition (US-Norm), tumors showing HER2 expression 3+ or amplification were considered HER2 positive. Results: 96 of 100 samples were eligible. Amplification was observed in 14.6% and 15.6% by SISH and IHC/SISH. 71.9% by IHC vs. 75.0% by IHC/SISH had no expression (0) and 10.4% (IHC vs. IHC/SISH) had weak (1+) HER2 expression. Moderate expression (2+) and overexpression (3+) were observed in IHC 6.3%/11.5% and IHC/SISH 6.3%/8.3%, respectively. There were high concordances in IHC assessment of cases with score 0 (94.8%; κ=0.87) and 3+ (96.9%; κ=0.83) and moderate concordances in 1+/2+ cases (89.6%; κ= 0.44 vs. 93.8%; κ=0.47). Rate of HER2 positivity was similar in standard or novel method. In EU Definition 14.6% vs. 10.4% (p=0.52) were positive, respectively, with very good concordance (95.8%; κ=0.81).Concordance between HER2 positivity in standard or novel method was very good (99.0%; κ=0.96) in US definition with no significant differences (17.7% vs. 16.7%; p=1). Conclusions: Gene-protein platform has been tested for first time in gastric carcinoma. Results showed that this novel platform can be a feasible alternative to single methods. Discrepancies in cases with weak or moderate HER2 expression can be a result of observer variability.

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 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

A prospective study of repeat endoscopic biopsy to identify HER2-positive tumors following an initial HER2-negative biopsy in unresectable or metastatic gastric cancer: Gasther-1.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 27-27 ◽  
Author(s):  
Yoon-Koo Kang ◽  
Sook Ryun Park ◽  
Young Soo Park ◽  
Jeong Hoon Lee ◽  
Baek-Yeol Ryoo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Metastatic Gastric Cancer ◽  
Tumor Location ◽  
Endoscopic Biopsy ◽  
Repeat Biopsy ◽  
Her2 Status ◽  
Her2 Positive ◽  
Initial Biopsy ◽  
Her2 Positivity

27 Background: The intratumoral heterogeneity of HER2 expression in gastric cancer (GC) is a major challenge for identifying patients (pts) who would benefit from anti-HER2 therapy. The aim of this study is to evaluate the significance of re-evaluation of the HER2 status by repeat endoscopic biopsy in pts with HER2-negative GC on initial endoscopic biopsy. Methods: Pts with unresectable or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma who would receive 1st line chemotherapy were eligible if the HER2 was negative on the initial endoscopic biopsy. HER2 positivity was defined as IHC 3+ or IHC 2+/FISH+ using the GC scoring system. A repeat endoscopic biopsy was performed in ≥6 different primary tumor sites immediately after obtaining initial HER2-negative results. Results: From May 2011 to April 2013, a total of 183 pts were enrolled. Baseline characteristics at the time of the initial biopsy were as follows: tumor location, GEJ~fundus/body~antrum/diffuse stomach = 22 (12.0%)/115 (62.9%)/46 (25.1%); Lauren classification, intestinal/diffuse/mixed = 53 (29.0%)/111 (60.7%)/19 (10.4%); and HER2 IHC score, 0/1/2 = 149 (81.4%)/26 (14.2%)/8 (4.4%). The median number of biopsy pieces was 5 (range, 1-15) and 10 (1-15) in the initial and repeat biopsy, respectively (p<0.0001). As HER2 positive tumor was identified in 16 pts, HER2 positivity rate on repeat biopsy was 8.7% (95% CI 4.6-12.8%). The detection of HER2 positivity on repeat biopsy was associated with tumor location (diffuse stomach vs others = 0% vs 11.7%, p=0.013), Bormann type (IV vs others = 0% vs 11.7%, p=0.013), and the HER2 IHC score on the initial biopsy (0 vs 1/2 = 6.7% vs 18.2%, p=0.045). In multivariate analysis, the HER2 IHC score (1/2 vs 0, OR = 3.30; p=0.041) was an independent predictor of HER2 positivity in repeat biopsy. Conclusions: In pts with metastatic or unresectable GC, repeat endoscopic biopsy could detect HER2-positive GC which initial biopsy had missed. As anti-HER2 therapy improves the survival of pts with HER2 positive GC, in pts who showed HER2 negativity on initial biopsy, repeat biopsy should be considered subsequently.

A novel method combining gene and protein platforms on one slide for the detection of HER2 in gastric cancer: Final results.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 19-19
Author(s):  
Dominique Werner ◽  
Achim Battmann ◽  
Kristina Steinmetz ◽  
Tobin Jones ◽  
Tiffany Lamb ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Adequate Treatment ◽  
New Gene ◽  
Feasible Alternative ◽  
High Concordance ◽  
Staining Methods ◽  
Novel Method

19 Background: The evaluation of gene amplification and/or protein overexpression of HER2 in gastric cancer is a prerequisite to establish an adequate treatment strategy. Gastric tumors are heterogeneous and separate evaluations lead to uncertainties in localizing distinct clones and are time consuming. The aim of this study was to evaluate the feasibility of gene-protein platform in comparison to single staining methods. Methods: Immunohistochemistry (IHC) plus silver in situ hybridization (SISH) (IHC/SISH) and the new gene-protein platform (gene/protein) method for HER2 were performed in randomly collected 100 cases of gastric carcinoma. Evaluation was performed by two observers, in discrepant cases a third observer was consulted to make a decision by consensus. Results of IHC and SISH were compared with gene/protein staining. Rüschoff criteria were applied. Tumors showing HER2 expression 3+ or amplification were considered HER2 positive. Results: 96 of 100 samples were eligible. Amplification was observed in 14.6% by both, conventional SISH and gene/protein platform. 70.8% by IHC and gene/protein had no expression (0) and 10.4%/11.5% (IHC vs. gene/protein) had weak (1+) HER2 expression. Moderate expression (2+) was observed in 9.4% by IHC and 7.3% by gene/protein. Rate of overexpression (3+) was similar in IHC (9.4%) and gene/protein (10.4%). There were complete concordances (100%; κ=1) in IHC assessment of cases with score 0 and SISH amplified tumors. High concordance are shown in score 1+ (98.96%; κ=0.947) and 3+ (96.88%; κ=0.825) cases. Concordance in cases with score 2+ was found in 95.83% (κ=0.728) of the observations. After third observation, there were 5 discordant cases with most discrepancies in assessment of IHC score 2+ or 3+. Conclusions: Gene-protein platform has been tested for first time in gastric carcinoma. Results showed that this novel platform can be a feasible alternative to single methods. Discrepancies in cases with moderate HER2 expression are a result of observer variability.

scholarly journals Mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after trastuzumab-based chemotherapy for HER2-positive gastric cancer: a case report

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Hiromi Nagata ◽  
Hironori Tsujimoto ◽  
Yoshihisa Yaguchi ◽  
Keita Kouzu ◽  
Yujiro Itazaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Rare Case ◽  
Metastatic Tumor ◽  
Endoscopic Biopsy ◽  
Her2 Status ◽  
Resected Specimen ◽  
Her2 Positive ◽  
Standard Regimen ◽  
Mixed Adenoneuroendocrine Carcinoma ◽  
Her2 Positivity

Abstract Background Trastuzumab (T-mab)-based chemotherapy is a standard regimen for human epithelial growth factor 2 (HER2)-positive gastric cancer. However, some patients have demonstrated a change in HER2 status after T-mab-based treatment of breast cancer. We report a rare case of mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after T-mab-based chemotherapy for HER2-positive gastric cancer. Case presentation A 60-year-old man presented with a mass of the upper abdomen, which was diagnosed as adenocarcinoma with a HER2 score of 3+ by endoscopic biopsy. He received seven cycles of combination chemotherapy with capecitabine, cisplatin, and T-mab. Subsequently, he underwent open total gastrectomy, distal pancreatosplenectomy, and extended left hepatic lobectomy as a conversion surgery. The surgically resected specimen demonstrated both adenocarcinoma and neuroendocrine components; therefore, it was diagnosed as HER2-negative mixed adenoneuroendocrine carcinoma. Although the patient received additional chemotherapy, multiple liver metastases appeared at 3 months postoperatively and he died at 6 months postoperatively because of the rapidly progressing metastatic tumor. Conclusions We encountered a rare case of rapidly progressive mixed adenoneuroendocrine carcinoma that was negative for HER2 expression after T-mab treatment combined with chemotherapy.

scholarly journals Loss of HER2 Positivity after Trastuzumab in HER2-Positive Gastric Cancer: Is Change in HER2 Status Significantly Frequent?

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yu Ishimine ◽  
Akira Goto ◽  
Yoshito Watanabe ◽  
Hidetaka Yajima ◽  
Suguru Nakagaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Residual Tumor ◽  
Her2 Status ◽  
Resected Specimen ◽  
Her2 Positive ◽  
Curative Intent ◽  
Course Of Disease ◽  
Trastuzumab Therapy ◽  
Her2 Positivity

Trastuzumab has recently been introduced as a treatment for HER2-positive metastatic and/or unresectable gastric cancer (MUGC); however, compared with breast cancer, some issues concerning HER2 and trastuzumab therapy for gastric cancer remain unclear. A 74-year-old woman received trastuzumab-containing chemotherapy for HER2-positive MUGC. She had a marked response to 8 months of chemotherapy, and gastrectomy and hepatic metastasectomy with curative intent were performed. The resected specimen showed complete loss of HER2 positivity in the residual tumor. For MUGC, a change in HER2 status during the course of the disease with or without chemotherapy has rarely been reported. However, in breast cancer, a significant frequency of change in HER2 status during the course of disease has been reported, and reevaluation of HER2 positivity in metastatic/recurrent sites is recommended. The choice of trastuzumab for MUGC is currently based on the HER2 status of the primary tumor at the time of initial diagnosis, without reassessment of HER2 status during the course of disease and/or in metastatic/recurrent sites, on the assumption that HER2 status is stable. However, our case casts doubt on the stability of HER2 in gastric cancer.

scholarly journals Loss of HER2 positivity after anti-HER2 chemotherapy in HER2-positive gastric cancer patients: results of the GASTric cancer HER2 reassessment study 3 (GASTHER3)

2018 ◽  
Vol 22 (3) ◽  
pp. 527-535 ◽  
Author(s):  
Seyoung Seo ◽  
Min-Hee Ryu ◽  
Young Soo Park ◽  
Ji Yong Ahn ◽  
Yangsoon Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Her2 Positive ◽  
Gastric Cancer Patients ◽  
Her2 Positivity

scholarly journals Differences in outcome according to chemotherapy backbone and maintenance treatment in HER2 positive metastatic gastric cancer (GC) or gastroesophageal junction (GEJ)

2018 ◽  
Vol 29 ◽  
pp. viii225
Author(s):  
N. Martinez Lago ◽  
S. Candamio Folgar ◽  
C. Grande Ventura ◽  
M. Salgado Fernandez ◽  
J. De la Camara Gomez ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Maintenance Treatment ◽  
Gastroesophageal Junction ◽  
Metastatic Gastric Cancer ◽  
Her2 Positive

Prognostic factors for survival in patients with advanced gastric cancer treated with chemotherapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 142-142
Author(s):  
Montserrat Mangas ◽  
Alberto Carmona Bayonas ◽  
Maria Luisa Sanchez Lorenzo ◽  
Avinash Ramchandani ◽  
Teresa Garcia ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Advanced Gastric Cancer ◽  
Group Performance ◽  
Gastroesophageal Junction ◽  
Cox Proportional Hazards Model ◽  
Her2 Status ◽  
Her2 Positive ◽  
Ecog Ps

142 Background: A prognostic model in advanced gastric cancer that integrates the Her2 status,histopathological classifications and other patient’s or treatment-dependent parameters is lacking. The aim is to identify clinicopathological factors for overall survival in a cohort of patients with advanced gastric cancer. Methods: 526 consecutive patients with advanced adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach were analyzed. All patients were treated with poly-chemotherapy ( ≥ 2 drugs) at 19 Spanish and one Chilean centers between 2012 and 2015. Characteristics of patients, tumors, therapies and pathological factors, were analyzed by a Cox proportional hazards model. Results: The median overall survival was 10.3 months [95% confidence interval (CI), 9.5-11.1], and the time to progression was 6.7 months (95% CI, 6.1-7.2). Independent prognostic factors associated with overall survival were: distal non-diffuse histopathological subtype (hazard ratio, (HR) 0.73), Her2 positive 3+ (HR 0.54), Her2 positive 2+ with FISH + (HR 0.68), surgery of metastases (HR 0.34), Eastern Cooperative Group performance status (ECOG PS) 2 (HR 2.5), ECOG PS 3 (HR 7.37), and only distant lymph node metastases (HR 0.63) (Table 1). Conclusions: We have identified clinicopathological prognostic factors that could be important to stratify advanced gastric cancer, with potential implications in research and treatment. [Table: see text]

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