scholarly journals High Concordance of HER2 Overexpression by Immunohistochemistry on Mucosal Biopsies and Resection in Gastric Adenocarcinoma

Author(s):  
Anand Katavil Venugopalan ◽  
Kripa Varghese ◽  
Dipti Masih ◽  
Inian Samarasam ◽  
Reuben Thomas Kurien ◽  
...  

Introduction: High expression of Human Epidermal growth factor Receptor 2 (HER2) is a predictive biomarker for the treatment of gastric carcinomas with targeted agents. Targeted therapy could improve the outcome of patients with gastric carcinoma overexpressing HER2. There is limited information on mucosal biopsies to characterise the HER2 expression status of a tumour. Aim: To study HER2 expression by Immunohistochemistry (IHC) in matched mucosal biopsies and surgical specimens in patients with gastric adenocarcinoma and to discover the level of concordance. Materials and Methods: This was a prospective observational study conducted in the Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India, for one year (1st July 2016 to 30th June 2017). The IHC for HER2 was performed on matched mucosal biopsies and corresponding gastrectomy specimens of 72 patients. The HER2 overexpression (HER2+) was defined by a score 3+ on IHC. The results were analysed using Statistical Package for the Social Sciences (SPSS) software and Chi-square test was done for statistical significance. Results: The overall HER2 positivity rate was 11.11% (8/72). The HER2 positive rates (score 3+) were 9.72% on biopsy (7/72) and 8.33% on resection (6/72). Five cases showed concordance of HER2 between mucosal biopsies and resection specimens, however the other three cases showed a discordance i.e., two mucosal biopsies showed HER2 positivity and one resection showed HER2 positivity. The concordance rate in this study was 95.83% between resection and mucosal biopsies. Among the eight HER2 positive cases, five cases showed good concordance. One case showed positive shift: HER2 score was 0 on the mucosal biopsy and HER2 score was 3+ on the resection. Two cases showed a negative shift: mucosal biopsy showed HER2 score 3+ and the resection HER2 score 0. All the three discordant cases had received Neoadjuvant Chemotherapy (NACT) and showed heterogeneous staining on the resection specimen. None of the five concordant cases had received NACT and three of the five resections showed heterogeneous staining pattern. Conclusion: To the best of the authors’ knowledge, this was the first study to compare HER2 expression in gastric adenocarcinoma in matched biopsies and the corresponding resections in India. There was concordance of HER2 expression in 69 cases and discordance in three. Differences between biopsy and resection HER2 expression could be explained by intra-tumoural heterogeneity and possibly by decreased HER2 expression after NACT. The HER2 analysis by IHC on both mucosal biopsy and resections could optimise the selection of trastuzumab-eligible patients in case of gastric adenocarcinoma.

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 ◽  
...  

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


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3057-3057
Author(s):  
P. J. Perik ◽  
M. N. Lub-De Hooge ◽  
P. L. Jager ◽  
M. A. De Korte ◽  
J. A. Gietema ◽  
...  

3057 Background: The monoclonal antibody trastuzumab, apart from antitumor effect, can induce cardiotoxicity, particularly when combined with anthracyclines. Myocardial HER2 upregulation may serve, transiently, as a compensatory mechanism induced by cardiac stress. Previously we showed in a xenograft model that 111In-DTPA-trastuzumab scintigraphy can detect HER2 positive lesions (Br J Pharmacol 2004;143:99–106) but that myocardial 111In-DTPA-trastuzumab uptake was found in only 1 of 17 anthracycline-pretreated HER2-positive metastatic breast cancer patients (ESMO 2004#50). This low number may be related to the long interval between anthracycline administration (median 11 months) and performed scan in these patients. To evaluate whether myocardial HER2 expression is induced by anthracyclines, we performed 111In-DTPA-trastuzumab scans in patients shortly after anthracycline treatment. Methods: Patients who completed 4–6 cycles of anthracycline-based chemotherapy (< 3 weeks after last dose) underwent gammacamera imaging 48 and 96 h after iv administration of 150 MBq 111In-DTPA-trastuzumab (5mg). Results: 10 anthracycline-treated patients, 8 as adjuvant breast cancer treatment and 2 for metastatic sarcoma have been enrolled. Myocardial 111In-DTPA-trastuzumab uptake was observed in 5/10 anthracycline-treated patients who all were without symptomatic cardiac dysfunction. Conclusions: Shortly after completion of anthracycline treatment myocardial HER2 overexpression was detectable in 50% of the patients. This may be a transient phenomenon. 111In-DTPA-trastuzumab scan after anthracycline treatment prior to adjuvant trastuzumab may identify patients more susceptible for trastuzumab-induced cardiotoxicity. This important observation may add to optimal timing of trastuzumab therapy i.e. when HER2/neu expression in the heart is negative (again). [Table: see text]


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 6-6
Author(s):  
G. Von Minckwitz ◽  
S. Darb-Esfahani ◽  
S. Loibl ◽  
J. B. Huober ◽  
H. Tesch ◽  
...  

6 Background: Adjacent ductal carcinoma in situ (DCIS) is in found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Methods: Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline-taxane-trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Results: Fifty nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (p=0.033). Presence of adjacent DCIS was an independent negative predictor of pCR (odds ratio 0.42 [95% CI 0.2-0.9], p=0.027). Adjacent DCIS area decreased from pre-treatment to surgery (r=0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r=0.892) and after treatment (r=0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (p=0.055). Conclusions: HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4100-4100
Author(s):  
Dominique Werner ◽  
Achim Battmann ◽  
Kristina Steinmetz ◽  
Tobin Jones ◽  
Michele Martinez ◽  
...  

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.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11043-11043 ◽  
Author(s):  
Julia Katharina Neugebauer ◽  
Brigitte Kathrin Rack ◽  
Bernadette Anna Sophia Jaeger ◽  
Ulrich Andergassen ◽  
Aurelia Pestka ◽  
...  

11043 Background: The discordance between HER2-expression on circulating tumor cells (CTC) in peripheral blood and the primary tumor has already been shown by our study group for early breast cancer patients with HER2-positive tumors. Here, we compare the results to CTC prevalence and HER2-status of CTC after adjuvant chemotherapy. Methods: The SUCCESS B trial compares FEC-Docetaxel vs. FEC-Docetaxel-Gemcitabine and HER2-targeted therapy as adjuvant treatment for patients with early, HER2-positive, node positive or high risk node negative primary breast cancer. We prospectively analyzed 23ml peripheral blood before and after chemotherapy. CTC and HER2-status were assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-CK 8/18/19, anti-CD45 antibodies as well as a fluorescein conjugate antibody for HER2-phenotyping. Cutoff for CTC positivity was ≥ 1 CTC. HER-positivity of CTC was assigned if at least one CTC showed strong HER2 staining (3+). Results: CTCs and their HER2-status both before and after chemotherapy were available for 392 patients. In 179 (45.7%) patients no CTC were detected before and after chemotherapy. CTC status changed from positive before to negative after chemotherapy in 104 (26.5%) patients and from negative before to positive after chemotherapy in 69 (17.6%) patients, while 40 (10.2%) patients had a consistently positive CTC status. Patients were significantly more likely to change their CTC status from positive to negative than from negative to positive (p = 0.01). Of the 40 patients with CTC both before and after chemotherapy, 14 (35%) patients had HER2-positive CTC before and after therapy, and 9 (22%) patients had HER2-negative CTC at both time points. 7 (18%) patients had HER2-positive CTC before but not after chemotherapy, while 10 (25%) patients showed the reverse pattern (p = 0.63). Conclusions: Cytotoxic treatment does not seem to influence the HER2-status on CTC. Follow-up data within the Success B trial will analyze the relevance of the HER2-expression of CTC to predict the efficacy of targeted treatment.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Kwang Kuk Park ◽  
Song I Yang ◽  
Kyung Won Seo ◽  
Ki Young Yoon ◽  
Sang Ho Lee ◽  
...  

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jan Trøst Jørgensen ◽  
Henrik Winther ◽  
Jon Askaa ◽  
Lena Andresen ◽  
Dana Olsen ◽  
...  

The development of trastuzumab (Herceptin®) was one of the most significant cancer drug development projects of the 20th century. Not only was it a scientific and medical achievement but it also paved the way for the drug-diagnostic codevelopment model, where a predictive biomarker assay is developed in parallel to the drug. One of the challenges in the development of trastuzumab was to select the right patient population likely to respond and here, it was critical to have access to an accurate, robust and reliable assay for detection of HER2 overexpression in tumors. In the clinical development of trastuzumab, a clinical trial assay (CTA), developed by Genentech, was used for selection of HER2 positive patients. However, during the phase III trial with trastuzumab, a new optimized IHC assay, HercepTest™ was designed and developed by Dako. In the final stage of its development, a comparative study with the CTA was conducted in order to show concordance between the two assays. In September 1998, the Food and Drug Administration (FDA) simultaneously granted approval to trastuzumab and HercepTest™. The assay has been used for patient selection in a number of significant breast cancer clinical trials such as the HERA, CLEOPATRA, EMILIA and more. In these trials, HercepTest™ demonstrated its clinical utility in the neoadjuvant, adjuvant, and metastatic setting as well as in relation to different types of HER2 targeted therapies. Likewise, the assay was used for selection of HER2 positive gastric cancer patients in the important ToGA trail. HercepTest™ was the first companion diagnostic ever approved by the FDA, and more than 20 years of use has documented its clinical impact.


2020 ◽  
Vol 7 (47) ◽  
pp. 2747-2751
Author(s):  
Lekshmi Vijayakumaran Nair Lilly ◽  
Geetha Sukumaran

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


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10535-10535 ◽  
Author(s):  
Saswati Hazra ◽  
Jeeyun Lee ◽  
Phillip Sangwook Kim ◽  
Kyoung-Mee Kim ◽  
Limin Liu ◽  
...  

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.


2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S39-S40
Author(s):  
Y Dimopoulos ◽  
M Sidawy

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.


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