scholarly journals Evaluation of HER2 by Automated FISH and IHC in Gastric Carcinoma Biopsies

2016 ◽  
Vol 31 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Maria R. Silva ◽  
Ana Alarcão ◽  
Teresa Ferreira ◽  
Maria d'Aguiar ◽  
Ana Ladeirinha ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Her2 Expression ◽  
Her2 Amplification ◽  
Bond System ◽  
Routine Procedures ◽  
Dual Probe ◽  
Her2 Positivity

Purpose The use of trastuzumab (Herceptin) to target HER2 has been applied in breast carcinoma and gastric carcinoma (GC). Previous studies have tested trastuzumab's effectiveness by assessing HER2 expression or HER2 amplification by means of immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). In this work we aimed to evaluate automated FISH and IHC technologies for HER2 detection in GC biopsies to be used in routine pathology practice. Methods The study used an Oracle HER2 IHC System and an LSI HER2/CEP17 Dual Probe on an automated Bond™ system (Leica Microsystems). One hundred GC biopsies were evaluated including 44 intestinal type, 38 diffuse type and 18 indeterminate type according to Lauren's classification. Results The overall concordance rate between the automated FISH and IHC methods was 94% ( κ = 0.87), as 6 samples were scored as equivocal (4 in IHC and 2 in FISH). Moreover, HER2 positivity was significantly different between the 3 types of GC (p<0.05), being more frequent in intestinal-type GC (23%) than in the other 2 histological types (5% and 0%). Finally, the HER2/CEP17 FISH ratio was significantly different (p<0.01) between disomic and polysomic samples, being higher in polysomic samples (mean 1.633 ± 0.509) than in disomic samples (mean 1.231 ± 0.675). Conclusions Automated HER2 testing of GC biopsies using the Leica Bond system was useful and efficient. This method allowed us to improve normal routine procedures, minimizing time and costs as well as handling and observation errors.

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.

scholarly journals Epithelial-mesenchymal transition in main types of gastric carcinoma

2021 ◽  
Vol 10 (2) ◽  
pp. 13-20
Author(s):  
I.V. Vasilenko ◽  
◽  
R.B. Kondratyk ◽  
I.S. Grekov ◽  
A.M. Yarkov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Mixed Type ◽  
Epithelial Mesenchymal Transition ◽  
Rapid Development ◽  
Tumor Formation ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Vimentin Expression ◽  
Mesenchymal Transition

Introduction. The rapid development of basic science enabled us to significantly expand our understanding of various intercellular interactions. Epithelial-mesenchymal transition (EMT) is known to play a key role in certain tissue formation in the embryonic period. However, recent data show that EMT can also be observed in some pathological conditions, in particular, in various neoplasm development. This suggests that there are a number of alternative and fundamentally new mechanisms for the tumor formation and progression. Thus, EMT, which occurs in carcinomas, increases the invasiveness, immunoresistance, immunity to therapy, and the metastatic potential. Knowledge of EMT features and their timely recognition in morphological tumor diagnosis is of great predictive importance for patients. The aim of the research was to study the morphologi-cal features of epithelial-mesenchymal transition in the main types of gastric cancer. Materials and methods. We studied specimens of gastric carcinomas (N=64) including 31 cases of diffuse type, 19 cases of intestinal type, and 14 cases of mixed type. Results. All cases of the diffuse carcinoma group showed spread EMT features, which appeared already in the mucosa and completed with positive vimentin expression in 93.5% of cases. The malignant cell prolifera-tive activity was low; however, in 29% of cases we detected areas of moderate or even high activity. In the intestinal type gastric cancer, EMT developed as a result of tumor progression, it arose more often in the deeper layers and was incomplete and focal. As a rule, the proliferative activity of tumor cells was high and moderate. Vascular invasion occurred more often in diffuse type (90.3%), less often in mixed type (71.4%), and even less often in the intestine type (55.8%) gastric carcinoma. Conclusion. The variety of morphological features of EMT, its frequency, prevalence, completeness, and sequence in the development of various types of gastric cancer determines the features of their clinical manifestation and influences their further management. Keywords: gastric cancer, diagnosis, histological main types, EMT, morphopathology

scholarly journals Novel markers to detect HER2 amplification in Breast cancer

2021 ◽  
Author(s):  
Shikha Mudgal ◽  
Arnav Kalra ◽  
Shalinee Rao ◽  
Bina Ravi ◽  
Nilotpal Chowdhury
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Predictive Biomarker ◽  
Gene Expression Omnibus ◽  
Surrogate Markers ◽  
Her2 Expression ◽  
Her2 Amplification ◽  
Reflex Testing ◽  
Geo Database

Overexpression of HER2 in breast cancer is an important prognostic and predictive biomarker, assessed using immunohistochemistry (IHC) and in situ hybridization (ISH). More than 20% of tumours are graded equivocal on IHC and is send for reflex testing via ISH. In situ hybridization (ISH) is an expensive assay and is not available widely in resource limiting areas. Therefore, we propose that genes found significantly co-expressed with HER2 in breast cancer can be used as surrogate markers for HER2 in breast cancer which can detect HER2 positivity on IHC itself. This hypothesis is based on analysis of publicly available datasets from the Gene Expression Omnibus (GEO) database. The genes found most significantly correlated with HER2 expression were PGAP3 (r = 0.85), GRB7 (r = 0.82), STARD3 (r = 0.78), CDK12 (r= 0.68), PSMD3 (r= 0.67) and GSDMB (r = 0.63). We hypothesize that these identified surrogate markers for HER2 amplification which can be detected on IHC can detect HER2 amplification status in HER2 equivocal tumors based on IHC staining alone and will reduce the number of HER2 2+ (equivocal) category tumours.

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

Prognostic Marker Expression In Microinvasive Breast Cancer

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S39-S40
Author(s):  
Y Dimopoulos ◽  
M Sidawy
Keyword(s):  
Prognostic Marker ◽  
Ductal Carcinoma ◽  
Her2 Expression ◽  
Her2 Positive ◽  
High Concordance ◽  
Marker Expression ◽  
Microinvasive Breast Cancer ◽  
Support Time ◽  
Her2 Positivity

Abstract Introduction/Objective Microinvasive breast carcinoma (Mi) is defined as invasive carcinoma (IC) less than 1 mm in greatest dimension. Depletion of the focus during further immunohistochemical investigation is commonly observed. Studies on prognostic marker expression report high concordance between the Mi and concomitant ductal carcinoma in-situ (DCIS). Compared to IC, Mi has a higher rate of Her2 positivity, indicating aggressive phenotype and potential variation in marker expression over time. We aimed to verify the concordance between Mi and DCIS in patients with pure Mi, as well as between foci of Mi and IC in patients with both. Methods A total of 21 cases of Mi and 9 cases with both IC and Mi disease were identified and evaluated for pathologic characteristics and ER, PR, and Her2 expression by immunohistochemistry. The rate of Her2 in Mi was compared to national benchmarks for IC. Results Mi was associated with high grade DCIS. 100% concordance of Her2 expression between Mi and DCIS was present in 14/21 cases where Mi was not depleted. Discrepancy between ER/PR was seen in two cases (Mi negative/DCIS focally positive). 50% of these Mi cases were Her2 positive, compared to the 13–25% generally reported for IC. Overall, by extrapolating Mi status from the concomitant DCIS when the Mi became depleted, 38% of Mi was positive for Her2. 100% concordance between foci of Mi and IC in patients presenting with both was observed. Conclusion Mi had a more aggressive prognostic marker phenotype compared to IC based on Her2 positivity. Concordance of prognostic marker expression between Mi and concomitant DCIS supports reporting of the DCIS status when the Mi becomes depleted, with only rare ER/PR discrepancies observed. Concordance between foci of Mi and IC in patients with both does not support time-based variation in marker expression. However, further investigation is warranted to uncover potential changes.

HER2 Overexpression and Amplification in Feline Pulmonary Carcinoma

2021 ◽  
pp. 030098582098814
Author(s):  
Luisa Vera Muscatello ◽  
Enrico Di Oto ◽  
Miriam Dignazzi ◽  
William J. Murphy ◽  
Ilaria Porcellato ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Her2 Overexpression ◽  
Fish Analysis ◽  
Her2 Expression ◽  
Her2 Amplification ◽  
Protein Overexpression ◽  
Her2 Protein

HER2 is overexpressed, amplified, and mutated in a subset of human lung cancer. The aim of this study was to investigate HER2 protein overexpression and gene amplification in feline pulmonary carcinomas. Thirteen pulmonary carcinomas were selected and TTF-1 and HER2 expression was evaluated by immunohistochemistry. Fluorescence in situ hybridization (FISH) was performed with a HER2 probe and a BAC probe for the feline chromosome E1p1.12-p1.11 region. Twelve adenocarcinomas and 1 squamous cell carcinoma were diagnosed. TTF-1 was positive in 7 carcinomas (58%). HER2 was overexpressed in 2 (15%), equivocal in 5 (38%), and negative in 6 cases (46%). FISH analysis of HER2 was indeterminate in 2 cases. Three pulmonary carcinomas (27%) had HER2 amplification and 8 cases were not amplified (73%). The significant correlation between HER2 protein overexpression and gene amplification are promising preliminary data, but study of additional cases is needed to confirm HER2 as a target for possible innovative treatments.

p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type

1999 ◽  
Vol 6 (8) ◽  
pp. 739-745 ◽  
Author(s):  
Franco Roviello ◽  
Daniele Marrelli ◽  
Carla Vindigni ◽  
Alfonso De Stefano ◽  
Donatella Spina ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Gastric Carcinoma ◽  
Intestinal Type ◽  
Diffuse Type
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