Establishment of primary gastric and gastroesophageal (GE) junction xenografts: A model for characterizing disease heterogeneity.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 51-51
Author(s):  
Yelena Yuriy Janjigian ◽  
Robert Mazgaj ◽  
Gregory Carbonetti ◽  
Laura H. Tang ◽  
Blake Hefter ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Rational Design ◽  
Growth Factor Receptor ◽  
Cytotoxic Agents ◽  
Her2 Positive ◽  
Disease Heterogeneity ◽  
Cancer Subtypes ◽  
Signet Ring ◽  
Aseptic Conditions

51 Background: Gastric cancer is a heterogeneous disease that may be subdivided into distinct subtypes—proximal/gastroesophageal (GE) junction, diffuse/signet ring type, and distal gastric cancers—based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology and gene expression. Human epidermal growth factor receptor (HER2) is a validated treatment target in gastric cancer. For patients with metastatic disease, the available cytotoxic agents are applied indiscriminately to all disease subtypes, and with only modest success. The purpose of this study is to establish xenograft models from gastric cancer subtypes to improve our understanding of disease heterogeneity and develop therapies geared for each subtype of gastric cancer. Methods: Fresh specimens obtained from resected primary or metastatic tumors under aseptic conditions. 1 g tumor samples injected SQ into flanks of NOD/SCID mice. Xenografts established after 5 passages and maintained by serial transplantation into new mice. Cell cultures established after 5 in vitro passages; cell lines after 15 passages. Results: To date 26 tumor samples have been implanted from which 8 xenografts have been established. Table below summarizes the results. Cell line established from HER2-positive, trastuzumab refractory tumor resected from brain metastasis. Conclusions: HER2-positive tumors have a favorable xenograft yield. Prior chemo or radiation therapy does not impact engraftment. Standard and experimental therapies are being tested on these xenografts to further validate difference in their biology and guide rational design of clinical trials. [Table: see text]

Establishment of esophagogastric xenografts: A model for characterizing disease heterogeneity.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 95-95
Author(s):  
Yelena Yuriy Janjigian ◽  
Christopher M. Gromisch ◽  
Gregory Carbonetti ◽  
Laura H. Tang ◽  
David Paul Kelsen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Rational Design ◽  
Single Agent ◽  
Cytotoxic Agents ◽  
Her2 Positive ◽  
Disease Heterogeneity ◽  
Esophagogastric Cancer ◽  
Xenograft Models

95 Background: Gastric cancer is a heterogeneous disease that may be subdivided into distinct subtypes—proximal/gastroesophageal (GE) junction, diffuse/signet ring type, and distal gastric cancer/intestinal type—based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology and gene expression. Human epidermal growth factor receptor (HER2) is a validated treatment target in gastric cancer. For patients with metastatic disease, the available cytotoxic agents are applied indiscriminately to all disease subtypes, and with only modest success. The purpose of this study is to establish xenograft models from gastric cancer subtypes to improve our understanding of disease heterogeneity and develop therapies geared for each subtype of gastric cancer. Methods: Fresh specimens obtained from resected primary or metastatic tumors under aseptic conditions. 1 g tumor samples injected SQ into flanks of NSG mice. Xenografts established after 5 passages and maintained by serial transplantation into new mice. Cell cultures established after 5 in vitro passages; cell lines after 15 passages Results: To date, 66 tumor samples have been implanted from which 16 xenografts have been established. The table below summarizes the results. Single-agent afatinib (pan-ErbB inhibitor) demonstrated antitumor activity in an HER2-positive xenograft established from MSKCC patient’s tumor harvested from a skin metastasis. Conclusions: We have established xenograft models of gastric cancer. In vivo testing of afatinib showed a reduction of tumor growth of HER2-positive gastric cancer. These models provide a platform to study potential therapeutics for esophagogastric cancer to further validate difference in their biology and guide rational design of clinical trials. [Table: see text]

scholarly journals Strengthening Gastric Cancer Therapy by Trastuzumab-Conjugated Nanoparticles with Simultaneous Encapsulation of Anti-MiR-21 and 5-Fluorouridine

2017 ◽  
Vol 44 (6) ◽  
pp. 2158-2173 ◽  
Author(s):  
Nan Hu ◽  
Jun Feng  Yin ◽  
Ze Ji ◽  
Yidong Hong ◽  
Puyuan Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cellular Uptake ◽  
Photoelectron Spectroscopy ◽  
Growth Factor Receptor ◽  
Double Emulsion ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Antitumor Effects

Background/Aims: MicroRNA-21 is an oncogenic miR (oncomiR) frequently elevated in gastric cancer (GC). Overexpression of miR-21 decreases the sensitivity of GC cells to 5-fluorouridine (5-Fu) and trastuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2). Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including anti-miRNA oligonucleotides (AMOs). This study is a continuation of earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target GC with HER2 receptor over-expression using anti-miRNA-21 (AMO-21) and 5-Fu. Methods: HER-PEG-PCL NPs were prepared by one-step carbodiimide coupling using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAc) and Sulfo-NHS in aqueous phase. Covalent coupling of amino groups at the surface of PEG-PCL with the carboxyl groups of trastuzumab was analyzed by X-ray photoelectron spectroscopy (XPS). AMO-21/5-Fu NPs were formulated by a double-emulsion solvent evaporation technique. The cell line specificity, cellular uptake and AMO-21 delivery were investigated through the rhodamine-B-labeled 6-carboxyfluorescein (FAM)-AMO-21-PEG-PCL NPs coated with or without the antibody in both Her2-positive (NUGC4) and negative GC cells (SGC7901) visualized by fluorescence microscopy. The cytotoxicity of the HER-PEG-PCL NPs encapsulating AMO-21 was evaluated by MTT and apoptosis. Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to examine miR-21 and phosphatase and tensin homolog (PTEN) and Sprouty2 expression in GC cell lines. The antitumor effects of AMO-21/5-Fu NPs were compared with other groups in xenograft gastric cancer mice. Results: The antibody conjugates significantly enhanced the cellular uptake of NPs. The AMO-21/5-Fu NPs effectively suppressed the target miRNA expression in GC cells, which further up-regulated PTEN and Sprouty2. As a result, the sensitivity of HER2-expressing gastric cancer to trastuzumab and 5-Fu were enhanced both in vitro and in vivo. The approach enhanced the targeting by trastuzumab as well as antibody-dependent cellular cytotoxicity (ADCC) of immune effector cells Conclusions: Taken together, the results provide insight into the biological and clinical potential of targeted AMO-21 and 5-Fu co-delivery using modified trastuzumab for GC treatment.

scholarly journals Imaging-Guided Therapy Simultaneously Targeting HER2 and EpCAM with Trastuzumab and EpCAM-Directed Toxin Provides Additive Effect in Ovarian Cancer Model

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3939
Author(s):  
Tianqi Xu ◽  
Anzhelika Vorobyeva ◽  
Alexey Schulga ◽  
Elena Konovalova ◽  
Olga Vorontsova ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor Receptor ◽  
Repeated Administration ◽  
Ovarian Cancer Cells ◽  
Her2 Positive ◽  
Efficient Treatment ◽  
Pseudomonas Exotoxin A ◽  
Epidermal Growth

Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression of human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM) in approx. 30% and 70% of ovarian cancers, respectively, allows for co-targeted treatment. The clinical efficacy of the monoclonal antibody trastuzumab in patients with HER2-positive breast, gastric and gastroesophageal cancers makes it readily available as the HER2-targeting component. As the EpCAM-targeting component, we investigated the designed ankyrin repeat protein (DARPin) Ec1 fused to a truncated variant of Pseudomonas exotoxin A with reduced immunogenicity and low general toxicity (LoPE). Ec1-LoPE was radiolabeled, evaluated in ovarian cancer cells in vitro and its biodistribution and tumor-targeting properties were studied in vivo. The therapeutic efficacy of Ec1-LoPE alone and in combination with trastuzumab was studied in mice bearing EpCAM- and HER2-expressing SKOV3 xenografts. SPECT/CT imaging enabled visualization of EpCAM and HER2 expression in the tumors. Co-treatment using Ec1-LoPE and trastuzumab was more effective at reducing tumor growth and prolonged the median survival of mice compared with mice in the control and monotherapy groups. Repeated administration of Ec1-LoPE was well tolerated without signs of hepatic or kidney toxicity. Co-treatment with trastuzumab and Ec1-LoPE might be a potential therapeutic strategy for HER2- and EpCAM-positive OC.

Amplification and expression of c-MET correlate with poor prognosis of patients with gastric cancer and upregulate the expression of PDL1

2021 ◽  
Vol 53 (5) ◽  
pp. 547-557
Author(s):  
Ya’nan Yang ◽  
Chenchen Wang ◽  
Congqi Dai ◽  
Xinyang Liu ◽  
Wenhua Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Positive Association ◽  
Her2 Positive ◽  
Kaplan Meier ◽  
Met Amplification ◽  
Amplification Rate ◽  
Cox Proportional Hazard Regression

Abstract The prognostic significance of c-MET in gastric cancer (GC) remains uncertain. In the present study, we examined the amplification, expression, and the prognostic value of c-MET, human epidermal growth factor receptor 2 (HER2), and programmed cell death 1 ligand 1 (PDL1), together with the correlations among them in a large cohort of Chinese samples. A total of 444 patients were included. The immunohistochemistry (IHC) and the dual-color silver in situ hybridization (SISH) were performed to examine their expression and amplification. Univariate and multivariate analyses were performed by the Cox proportional hazard regression model, and survival curves were estimated by the Kaplan–Meier method. The positivity determined by IHC of c-MET was 24.8%, and the MET amplification rate was 2.3%. The positivity rates of HER2 and PDL1 were 8% and 34.7%, respectively. PDL1 expression had a significantly positive association with c-MET expression. c-MET positivity played a significant prognostic role in disease-free survival (DFS) (P = 0.032). Patients with mesenchymal-epithelial transition (MET) amplification had significantly poorer prognosis on both DFS and overall survival (OS). Subgroup analysis showed that in HER2-negative patients, but not in HER2-positive patients, MET-positive patients had significantly worse DFS (P = 0.000) and OS (P = 0.006). c-MET regulated the expression of PDL1 through an AKT-dependent pathway. c-MET inhibitor enhanced the T-cell killing ability and increased the efficacy of PD1 antibody. c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.

scholarly journals Trastuzumab-Modified Gold Nanoparticles Labeled with 211At as a Prospective Tool for Local Treatment of HER2-Positive Breast Cancer

Nanomaterials ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 632 ◽  
Author(s):  
Łucja Dziawer ◽  
Agnieszka Majkowska-Pilip ◽  
Damian Gaweł ◽  
Marlena Godlewska ◽  
Marek Pruszyński ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Local Treatment ◽  
Growth Factor Receptor ◽  
Dark Field ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Biological Studies ◽  
Positive Breast Cancer

Highly localized radiotherapy with radionuclides is a commonly used treatment modality for patients with unresectable solid tumors. Herein, we propose a novel α-nanobrachytherapy approach for selective therapy of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This uses local intratumoral injection of 5-nm-diameter gold nanoparticles (AuNPs) labeled with an α-emitter (211At), modified with polyethylene glycol (PEG) chains and attached to HER2-specific monoclonal antibody (trastuzumab). The size, shape, morphology, and zeta potential of the 5 nm synthesized AuNPs were characterized by TEM (Transmission Electron Microscopy) and DLS (Dynamic Light Scattering) techniques. The gold nanoparticle surface was modified by PEG and subsequently used for antibody immobilization. Utilizing the high affinity of gold for heavy halogens, the bioconjugate was labelled with 211At obtained by α irradiation of the bismuth target. The labeling yield of 211At was greater than 99%. 211At bioconjugates were stable in human serum. Additionally, in vitro biological studies indicated that 211At-AuNP-PEG-trastuzumab exhibited higher affinity and cytotoxicity towards the HER2-overexpressing human ovarian SKOV-3 cell line than unmodified nanoparticles. Confocal and dark field microscopy studies revealed that 211At-AuNP-PEG-trastuzumab was effectively internalized and deposited near the nucleus. These findings show promising potential for the 211At-AuNP-PEG-trastuzumab radiobioconjugate as a perspective therapeutic agent in the treatment of unresectable solid cancers expressing HER2 receptors.

Management of early-stage breast cancer: Are we headed in the right direction?

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 284-284
Author(s):  
U. Zurawska ◽  
D. A. Baribeau ◽  
C. Victor ◽  
S. Giilck ◽  
A. Florescu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Histological Grade ◽  
Growth Factor Receptor ◽  
Early Stage Breast Cancer ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Excellent Outcome ◽  
Hormone Receptor Positive ◽  
The Right

284 Background: The understanding of breast cancer (BC) as a heterogeneous disease consisting of distinct subtypes based on variation in expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) has led to more personalized treatment. We postulated that with increased adoption of chemotherapy and targeted therapy for HER2 positive patients, the outcomes of ER/PR+, HER2- and of HER2+ subtypes of breast cancer would be similar. Methods: A chart review was performed of female patients >18 years old seen by a medical oncologist at an academic cancer centre in Toronto, Canada, between January 1, 2005 and December 31, 2006, for stage I-III invasive breast cancer. Clinical features, 5-year overall (OS) and relapse-free survival (RFS) of three BC subtypes were compared: ER/PR+, HER2- (hormone receptor positive, HR), HER2+ (HER2), and ER/PR-, HER2- (triple negative, TN). Results: Of 870 patient charts reviewed, 525 were analysed. There were 341 HR, 101 HER2 and 83 TN patients. TN patients were younger (p<0.001), and had higher stage (p<0.001) and higher histological grade tumors (p<0.001). The 5-year RFS and OS were: HR: 88.2% and 96.6%, HER2: 76.7% and 92%, TN: 79.8% and 83.9%. Chemotherapy was used in 41.1%, 84.2% and 83.1% of HR, HER2 and TN patients. Anthracycline plus taxane regimens were used in 48.6%, 52.9% and 68.1% of HR, HER2 and TN patients, respectively. Among HER2 patients, only 74.3% received trastuzumab. The 5-year RFS and OS for HER2 patients who received trastuzumab were 79.9% and 91.8%, and for those who did not: 69% and 91.6%. Conclusions: HR+ patients have an excellent outcome. Despite significant improvement in outcomes of HER2+ patients with early stage breast cancer, they still remain at higher risk of recurrence along with TN patients. Trastuzumab was underutilized among HER2+ patients in this cohort, which may have contributed to decreased 5 year RFS. Ongoing prospective follow up of early BC outcomes by breast cancer subtypes is important.

Apatinib to enhance chemosensitivity of gastric cancer to paciltaxel and 5-fluorouracil.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15545-e15545
Author(s):  
Xiangdong Cheng ◽  
Zhiyuan Xu ◽  
Jiahui Chen ◽  
Chunli Zhang ◽  
Jianfa Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Late Stage ◽  
Zebrafish Embryo ◽  
Xenograft Model ◽  
Cytotoxic Agents ◽  
Pathological Examination ◽  
Conversion Surgery ◽  
Synergistic Interactions

e15545 Background: Patients (pts) with late-stage gastric cancer (GC) have a poor prognosis. Targeted agent combined with chemotherapy is expected to yield clinical benefits. Apatinib, a novel tyrosine kinase inhibitor targeting VEGFR-2, improves outcomes in patients with metastatic GC as a third line of treatment. Hence, we aimed to assess the efficacy and safety of apatinib plus chemotherapy in vivo and in vitro. Methods: The MGC803 cell viability was assessed by CCK-8 assay, and the interactions between apatinib and conventional cytotoxic agents revealed by combined index (CI) values were calculated using Calcusyn 2.0 software. We also used a zebrafish embryo xenograft model to validate the synergistic interactions. Furthermore, 4 pts with late-stage GC were enrolled to receive paclitaxel (PTX)/S1 chemotherapy plus apatinib in conversion surgery. Apatinib was administered 500 mg once a day continuously, PTX 130 mg/m2 was given on day 1, and S-1 was administered at 80 mg/m2for 14 consecutive days, followed by 7 days of rest. Treatment was administered for 3-5 cycles, but the last cycle did not include apatinib. Results: Apatinib showed synergistic interactions with both PTX and 5-Fu in vivo (CIs < 1). The zebrafish embryo xenograft model also demonstrated that addition of 0.25 µg/mL apatinib significantly enhanced the tumor growth inhibition effects of 25 (38.39% vs. 11.77%, P < 0.001) and 50 ng/fish (43.58% vs. 17.88%, P < 0.05) 5-Fu, as well as those of 0.75 ng/fish (53.62% vs. 35.22%, P < 0.001) and 1.5 ng/fish (59.71% vs.46.73%, P < 0.01) PTX. Apatinib plus S1/paclitaxel chemotherapy was well tolerable before surgery. Objective response to preoperative SPA treatment was achieved in all pts. No posteroperative bleeding event or wound-healing complication was observed. No postoperative mortality occurred and morbidity was encountered. Pathological examination showed that all pts had grade Ib pathological response. Conclusions: The experimental data suggested that apatinib improves the efficacy of PTX and 5-Fu both in vitro and in vivo. Clinical evidence showed that combination of PTX/S1 chemotherapy with apatinib has promising efficacy and acceptable safety profile in late-stage GC, especially in the conversion surgery.

Efficacy of cytotoxic agents after progression of anti-PD-(L)1 antibody for pretreated metastatic gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 152-152
Author(s):  
Kyoko Kato ◽  
Yukiya Narita ◽  
Seiichiro Mitani ◽  
Kazunori Honda ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Univariate Analysis ◽  
Patient Characteristics ◽  
Metastatic Gastric Cancer ◽  
Cytotoxic Agents ◽  
Her2 Positive ◽  
Period Range ◽  
Median Period ◽  
Metastatic Sites ◽  
Ecog Ps

152 Background: The efficacy of anti-PD-1 antibody for metastatic gastric cancer (mGC) was revealed. In non-small cell lung cancer (NSCLC), it was reported that overall response rate (ORR) in patients (pts) treated with chemotherapy (CTx) after immunotherapy exposure was higher than historical data from the pre-anti-PD-(L)1 era. The purpose of this retrospective study was to evaluate whether CTx improved efficacy outcomes after exposure anti-PD(L)1 antibody in mGC. Methods: We investigated retrospectively clinical characteristics at baseline of mGC pts who received CTx after progression of anti-PD-(L)1 antibody between April 2014 and August 2017. Anti-PD-(L)1 antibody was adapted as third- or later-line therapy. Pts fulfilled following criteria: histologically proven adenocarcinoma; ECOG PS 0-2; adequate organ functions; and received CTx including fluoropyrimidines (FU), platinum, and taxane or irinotecan. We evaluated efficacy outcomes, including ORR, disease control rate (DCR), time to treatment failure (TTF), and overall survival (OS). Results: Out of 40 treated with anti-PD-(L)1 antibody, 15 pts were included. Patient characteristics were as follows: median age (range), 67 (46-83) years; male/female, 13/2; ECOG PS (0/1/2), 5/8/2; HER2 positive, 8; histology (differentiated/undifferentiated), 10/5; metastatic lesions (peritoneum/liver/lung), 4/8/3; number of metastatic sites (1/≥2), 2/13; number of prior CTx regimens (3/4/5), 2/9/4; median period (range) from first line CTx, 30.7 (12.7-68.1) months; and CTx regimens (FU+oxaliplatin/taxane/irinotecan), 10/3/2. ORR, DCR, median TTF, and OS were 33% (95% CI, 15.2-58.3), 87% (95% CI, 62.1-96.3), 3.5 (95% CI, 1.6-4.4) months, and 7.6 (95% CI, 4.4-8.5) months, respectively. There were no predictive and prognostic factors associated with ORR, TTF, and OS on univariate analysis. At the beginning of CTx, 4 pts had immune-related adverse events (irAEs), but these were manageable and no new irAEs appeared during CTx. Conclusions: Our data support further evaluation of the use of CTx after progression of anti-PD-L 1 antibody, even in heavily pretreated mGC pts. Updated results will be presented.

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

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