Integrin β5 in plasma-derived exosomal protein predicting liver-specific metastasis in advanced gastric cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14521-e14521
Author(s):  
Qian Li ◽  
Xiaojing Xu ◽  
Yiyi Yu ◽  
Wei Li ◽  
Li Liang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Liver Metastasis ◽  
Cancer Metastasis ◽  
Tumor Tissue ◽  
Clinical Samples ◽  
Her2 Status ◽  
Enzyme Linked Immunosorbent Assay ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Frequent Event

e14521 Background: Gastric cancer (GC) is the second leading cause of cancer death in China. Liver metastasis (LM) is a highly frequent event of the advanced GC, and the patients with LM always present dismal prognosis. A predicted factor of LM is urgently established to screen out the population in high risk of LM. Tumor-derived exosomes play critical roles in cancer metastasis process. Exosomes integrin (ITG) αvβ5 is uptake by liver resident cells and linked to LM in cell lines. This study is designed to evaluate the association between exosomes ITG αvβ5 and liver metastasis, especially in HER2 positive gastric cancer. Methods: 74 untreated advanced GC patients with matched blood and tumor tissue samples and clinical features were collected in the study. Exosomal HER2, ITG αv and β5 expression were measured by enzyme-linked immunosorbent assay (ELISA) after the exosomes isolated from plasma. HER2 status of tumor tissue was determined by IHC and/or FISH. Results: Based on HER2 status of tumor tissue, we initially proved the feasibility of detecting HER2 expression from exosome. ROC curves showed the optimum exosomal HER2 expression diagnostic cutoff for HER2 positive patients was 266.38 pg/ml (sensitivity 71.4% and specificity 72.6%). In total, 27 patients were LM and the rest (n = 47) was non-LM. The median expression value of ITG αv and β5 were 57.55 pg/ml and 836.00 pg/ml, respectively. And these two median value were identified as the cutoff value for subsequent analysis, respectively. HER2 expression was merely linked to ITG β5 expression (P = 0.019), not ITG αv (P > 0.050). There was no relationship between ITG αv and LM (P = 0.629), however, ITG β5 expression presented significant association with LM (P = 0.016). We further probed the relationship between ITG and other metastasis. Results showed no correlation between any ITG and other non-liver organic metastases, like lung, bone, ovarian, lymph, and peritoneal metastasis. Besides, ITG β5 expression was also associated with LM in the HER2-positive GC patients. Conclusions: Exosomes might serve as a potential non-invasive diagnostic and screening tool. In clinical samples, ITG β5, not αv, was linked to LM, and might be a valuable biomarker in the use of predicting LM of GC, even in the HER2-positive patients.

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.

Differential HER2 expression in resected gastric cancer: Is there prognostic value?

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 54-54
Author(s):  
Sarah B. Fisher ◽  
Kevin E. Fisher ◽  
Malcolm Hart Squires ◽  
Sameer H. Patel ◽  
David A. Kooby ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Differential Expression ◽  
Tumor Size ◽  
Prognostic Value ◽  
Lymphovascular Invasion ◽  
Advanced Disease ◽  
Her2 Status ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Resectable Gastric Cancer

54 Background: For advanced gastric cancer, the ToGA trial established HER2 as an important therapeutic target in the 20% of patients whose tumors exhibited HER2 overexpression or gene amplification. Others have reported that HER2-positive tumors are associated with poor survival in advanced disease. The expression profile and prognostic value of HER2 in resectable gastric cancer are unknown. Methods: 111 pts underwent curative intent resection of gastric adenocarcinoma between 1/00-6/11 and had tissue available for analysis. Immunohistochemistry (IHC) for HER2 was performed on banked tumor specimens and graded by two pathologists blinded to outcomes utilizing ToGA trial criteria. An IHC score of 0+ or 1+ was regarded as negative, 3+ as positive. Fluorescence in-situ hybridization (FISH) for HER2 was performed on equivocal (2+) IHC samples. Primary outcome was differential expression, secondary outcome was overall survival (OS). Results: Median age was 64 years, 54% were male. Median tumor size was 4 cm, 7.2% had a positive margin, 67.6% were poorly differentiated, 23.4% had perineural invasion, 35.1% had lymphovascular invasion, and 61.3% had nodal metastases. 24 patients had stage I disease (21.6%), 32 stage II (28.8%), and 55 stage III (49.6%). Mean follow-up was 28.9 months, median OS was 27.2 months. HER2 expression by IHC was negative in 61 (55%), equivocal in 37 (33.3%), and positive in 13 (11.7%). Of the 37 equivocal cases, FISH was positive in 8, for a total of 21 HER2-positive cases (18.9%) and 90 HER2-negative cases (81.1%). HER2 status did not correlate with T or N stage, tumor size or location, tumor grade, or perineural or lymphovascular invasion. HER2 status was not associated with OS (p=0.36). Conclusions: Resectable gastric cancer exhibits differential expression of HER2, similar to that of advanced disease. Despite reports suggesting HER2 positive status is associated with aggressive disease and worse outcomes in the advanced setting, HER2 status is not associated with adverse pathologic factors or survival in resectable disease. Although not prognostic, the predictive value of HER2 status for response to trastuzumab in the adjuvant setting requires further investigation.

Detection and HER2 expression of circulating tumor cells in advanced gastric cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10541-10541
Author(s):  
Satoshi Matsusaka ◽  
Keisho Chin ◽  
Mariko Ogura ◽  
Mitsukuni Suenaga ◽  
Eiji Shinozaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Her2 Status ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Cellsearch System ◽  
Primary Tumors ◽  
Gastric Cancer Patients

10541 Background: This study was aimed at detecting and HER2-expressiong circulating tumor cells (CTC) in peripheral blood of chemo-naïve or chemo-resistant patients with advanced gastric cancer. Methods: All patients were enrolled using institutional review board-approved protocols at the Cancer Institute Hospital in the Japanese Foundation for Cancer Research and provided informed consent. The study population consisted of patients of age 18 years or older with histologically proven advanced gastric cancer. A total of 140 patients with advanced gastric cancer were enrolled into a prospective study. We used CellSearch system for detection and HER2 expression for CTC. Results: We detected ≥1 CTC/7.5ml in 80 of 140 patients (57.1%). HER2-positive CTC were observed in 19 of 80 CTC-positive patients (23.8%), including 6 patients with HSR2-negative primary tumors. 21 patients with HER2-positive primary tumors administered trastuzumab in combination with chemotherapy (Xeloda+cisplatin; 15, weekly Paclitaxel; 5). We detected ≥1 CTC/7.5ml at the baseline in 11 of 20 patients with trastuzumab treatment. HER2-positive CTCs were observed in 6 of 11 CTC-positive patients (54.5%). Patients with HER2-positive CTC at the baseline were shorter PFS than those with HER2-negative CTC at the baseline. Conclusions: HER2 expression on CTC was associated with chemo-resistance. Information on the HER2 status of CTC might be helpful for stratification of HER2-directed therapies.

Changing HER2-status of the primary gastric tumor after neoadjuvant trastuzumab-based therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16529-e16529
Author(s):  
Rashida Orlova ◽  
Natalia P. Beliak ◽  
Svetlana Kutukova ◽  
Natalia V. Zhukova ◽  
Inna Avramenko ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cells ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Residual Tumor ◽  
Her2 Status ◽  
Her2 Expression ◽  
Her2 Positive

e16529 Background: Aproximetly 16 % of patients with metastatic gastric cancer (GC) have HER2+ tumors. With localized stages, the detection rate of HER2+ is known to be lower. Addition of trastuzumab (T) to chemotherapy (CT) improved survival in metastatic, HER2+ GC. Unlike the metastatic disease, Her-2 did not represent an independent prognostic biomarker for early stages during exploratory analysis of MAGIC trial. The aim of the study was to compare human epidermal growth factor receptor 2 (HER2) expression before and after trastuzumab-based chemotherapy in patients with locally advanced HER2-positive gastric cancer, to evaluate the contribution of trastuzumab to the effectiveness of neoadjuvant treatment in this rare patient population. Methods: We assessed HER2 expression using immunohistochemistry in pre-treatment biopsied specimens and post-treatment resected specimens obtained from 10 patients with locally advanced HER2-positive (3+) gastric cancer receiving trastuzumab-based neoadjuvant chemotherapy: 8 men (80%) and 2 women (20%), from 30 to 80 years old, the median age was 63,5 years. Included 7 patients with resectable adenocarcinoma of the stomach and 3 patients with adenocarcinoma of the esophageal-gastric junction. All patients received neoadjuvant therapy with trastuzumab (100%) + chemotherapy: FLOT (2 patients), FOLFOX (7 patients), XELOX (1 patient). All patients underwent R0 gastrectomy. Tumor regression grading (TRG) after treatment were determined according to Mandard system. Results: Two patients showed a complete pathomorphological response of the tumor (20%,TRG1), therefore, the determination of postoperative HER2 status was not possible. Two patients (20%) maintained the HER2-positive status and six patients (60%) had a change in HER2 expression from positive to negative. Three patients had a (y)pT3 and 5 had a (y)pN+ tumor. Basing on histological changes the tumor regression TRG3 ( < 10% residual tumor cells) was observed in 5 patients (50%). TRG 4-5(preponderance of tumor cells/tumors without changes of regression) observed in 3 patients (30%). The follow-up period is too short for disease-free survival or overall survival to be assessed. Conclusions: HER2 expression can change after trastuzumab-based chemotherapy in patients with locally advanced HER2-positive gastric cancer. Continuous monitoring of HER2 expression after neoadjuvant treatments may be utilized to determine whether the continued use of trastuzumab is advisable.

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

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.

Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer: Results from the GeparQuattro study (GBG 40).

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 6-6
Author(s):  
G. Von Minckwitz ◽  
S. Darb-Esfahani ◽  
S. Loibl ◽  
J. B. Huober ◽  
H. Tesch ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Complete Eradication

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.

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.

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