scholarly journals Relative Prognostic Value of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Operable Oesophagogastric Cancer

ISRN Surgery ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
David S. Y. Chan ◽  
Fiona Campbell ◽  
Paul Edwards ◽  
Bharat Jasani ◽  
Geraint T. Williams ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
High Specificity ◽  
Endoscopic Biopsy ◽  
Receptor Expression ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Predictive Values

Aims. The aim of this study was to determine the prognostic significance of HER2 receptor expression in operable oesophagogastric adenocarcinoma. Methods. Eighty-five consecutive patients diagnosed with oesophagogastric adenocarcinoma [18 oesophageal (OC), 32 junctional (JC) and 35 gastric (GC)] undergoing potentially curative resection were studied retrospectively. Immunohistochemistry was used to determine HER2 status at endoscopic biopsy and resection specimen. The primary outcome measure was survival. Results. Twenty (24%) patients had HER2 positive tumours which was commoner in JC (14/32, 44% versus 2/18, 11% in OC and 4/35, 11% in GC, P=0.003). The sensitivity, specificity, positive and negative predictive values of HER2 status at endoscopic biopsy were 56%, 93%, 63%, 91% respectively (weighted Kappa=0.504, P<0.0001). Five-year survival in OC HER2 positive negative was 100% and 36% (P=0.167) compared with 14% and 44% (P=0.0726) in JC and 50% and 46% (P=0.942) in GC respectively. Conclusions. Endoscopic biopsy had a high specificity and negative predictive value in determining HER2 status. Patients with JC had a significantly higher rate of HER2 overexpression and this was associated with a nonsignificant poorer survival trend. A larger study is needed to confirm these findings because of the implications for neoadjuvant and adjuvant chemotherapy regimens.

scholarly journals Prognostic significance of receptor expression discordance between primary and recurrent breast cancers: a meta-analysis

2021 ◽  
Author(s):  
Sho Shiino ◽  
Graham Ball ◽  
Binafsha M. Syed ◽  
Sasagu Kurozumi ◽  
Andrew R. Green ◽  
...  
Keyword(s):  
Distant Metastasis ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Outcome Data ◽  
Receptor Expression ◽  
Her2 Status ◽  
Breast Cancers ◽  
Recurrent Tumors ◽  
Recurrent Breast

Abstract Purpose This meta-analysis aimed to investigate whether receptor (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]) discordances between primary and recurrent breast cancers affect patients’ survival. Methods Search terms contained ER, PR, and HER2 status details in both primary and recurrent tumors (local recurrence or distant metastasis) in addition to survival outcome data (overall survival [OS] or post-recurrence survival [PRS]). Results Loss of ER or PR in recurrent tumors was significantly associated with shorter OS as compared with receptor-positive concordance (hazard ratio [HR], 1.67; 95% confidence interval [% CI] 1.37–2.04; p < 0.00001 and HR, 1.45; 95% CI 1.21–1.75; p < 0.0001, respectively). Similar trends were observed in groups with only distant metastasis. Gain of ER was a significant predictor of longer PRS as compared with receptor-negative concordance (HR, 0.76; 95% CI 0.59–0.97; p = 0.03). Gain of PR was not a significant predictor of longer survival compared with receptor-negative concordance, but it could be related to better OS at distant metastasis. Both HER2 of loss and gain could be related to poor outcomes. Conclusion This meta-analysis showed that receptor conversion in recurrent tumors may affect patient survival as compared with receptor concordance.

Metastatic breast cancer: A regional audit of HER2 testing and trastuzumab access

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6097-6097
Author(s):  
P. Scullin ◽  
A. T. Drake ◽  
V. M. Coyle ◽  
J. J. McAleer
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Number Of Patients

6097 Background: Clinical trials have clearly established that patients receiving taxane-based chemotherapy for metastatic breast cancer (MBC) should be treated with trastuzumab if their tumour is shown to overexpress the human epidermal growth factor receptor 2 (HER2) receptor. This is based on median survival gains for patients with HER2 positive tumours treated with trastuzumab plus taxane chemotherapy compared to taxane alone. Methods: Patients commencing chemotherapy for MBC in Northern Ireland in 2004 were identified from pharmacy records. Their case notes were retrospectively reviewed to determine whether patients in routine clinical practice had HER2 testing and trastuzumab treatment if indicated. Results: One hundred and fifty six patients commenced chemotherapy, of whom 145(93%) had HER2 testing. In 69(44%) patients the HER2 result was already available at the time of this relapse. In the remaining 76(49%) patients the result became available in a median of 41.5 (range 0–368) days. Of those tested, 48 patients (33%) were HER2 positive (immuno-histochemistry 3+ or fluorescence in situ hybridization positive). Thirty eight of these patients were treated with trastuzumab, either as a single agent or in combination with chemotherapy. There were valid reasons for trastuzumab omission in 7 of 10 patients not given trastuzumab (4 given first line anthracycline-based regimen, 1 had cardiac dysfunction, 1 had extensive lung metastastes and 1 was unfit for treatment). The data were examined for variations in chemotherapy and trastuzumab use across the 4 health boards which comprise the region. The number of patients commencing chemotherapy ranged from 6.9 to 11.4 patients per 100,000 population indicating a significantly different utilisation (p<0.001). Conclusions: In our region 145 of 156 patients who received chemotherapy for MBC were tested for overexpression of the HER2 receptor (93%). Of those patients who were eligible to receive trastuzumab 31 out of 34 (91%) received trastuzumab. There were inequalities in the region regarding chemotherapy for MBC and the time required to obtain a HER2 result averaged 41.5 days. Testing of HER2 status at time of original diagnosis would streamline management of metastatic disease. No significant financial relationships to disclose.

Incidence and prognostic significance of HER2 overexpression in gastric cancer (GC): A monoinstitutional retrospective analysis.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 160-160
Author(s):  
Ferdinando De Vita ◽  
Michele Orditura ◽  
Alessio Fabozzi ◽  
Maria Maddalena Laterza ◽  
Jole Ventriglia ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Primary Tumor ◽  
Prognostic Significance ◽  
Gastric Body ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Tumor Site ◽  
First Line ◽  
Her2 Positive ◽  
Primary Tumor Site

160 Background: HER2 overexpression in GC is reported in 20% of cases; it is considered a negative prognostic factor with a positive predictive value of response to trastuzumab. We reviewed our case records analyzing its clinical significance. Methods: We retrospectively collected the data for patients (pts.) with histologically confirmed GC and tumor specimens. Results: From June 2011 to December 2012 we analyzed HER2 status in 76 pts with metastatic GC. (M/F 50/26, median age 64 years, ECOG performance status 0/1/2 = 59/12/5, G1/G2/G3 = 6.6%/22.4%/71%). In 36.8% of pts. gastric body was the primary tumor site. HER-2 overexpression was observed in 13 pts (17.1%). HER2-positive group had the following characteristics: M/F = 10/3, median age 63 years; Lauren’s histotype: 75% intestinal and 25% diffuse; G1/G2/G3 = 15.4%/30.8%/53.8%; T3-T4 tumors and N+ disease were observed in 46.1% respectively; the primary tumor site was: proximal 38.4%, distal 61.6%. 46.1% of pts with metastatic disease received a first line CT with a median progression free survival (mPFS) of 5 months (range, 3-7) and a median overall survival (mOS) of 9 months (range, 3-23). In HER2-negative group, (N= 63, M/F = 40/23, median age 64 years), 92.1% of pts. Lauren’s histotype: 45.5% intestinal and 54.5% diffuse; G1/G2/G3 = 4.8%/20.6%/74.6%; metastatic disease: 55.5%. T3-T4 tumors were assessed in 65.1% of pts and N+ disease in 61.9%. The primary tumor location was: proximal 38.1%, distal 61.9%. 57.1% with advanced disease received a first line CT with a mPFS of 5.5 months (range, 2-30) and a mOS of 10 months (range, 2-67). No statistically significant differences for mPFS (p: 0.08) and mOS (p: 0.06) were observed between HER2 positive and HER2 negative metastatic patients. Conclusions: According to our experience, HER2 overexpression doesn’t seem to correlate with a worse prognosis. In particular, it is not correlated with a worse histology and higher stage at diagnosis. Furthermore, no differences in terms of mPFS and mOS were observed between HER2 positive and HER2 negative metastatic pts.

scholarly journals Detection of HER2 expression and its structural alterations in gastric cancer tissues infected with cagA+ H. pylori

2020 ◽  
Author(s):  
Akhileshwar Kumar Srivastava ◽  
Divya Singh
Keyword(s):  
Gastric Cancer ◽  
Growth Factor Receptor ◽  
Pcr Amplification ◽  
Receptor Expression ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Gastric Cancer Cells ◽  
H Pylori ◽  
Cancer Tissues

AbstractBackgroundHelicobacter pylori (HP) cagA is the causing agent for development of gastric cancer (GC). H. pylori also involves to trigger the EGFR (epidermal growth factor receptor) expression in gastric cancer cells. However, the prognostic relation of cagA with HER2 status in GC was not well understood.ObjectiveThe main aim of this study was to investigate the link of HER2 expression with CagA+ H. pylori in GC tissues.Materials and MethodsThe study was performed on 85 GC tissues of GC patients. The specific primers of 16S rDNA and cagA for PCR amplification were used. For investigation of HER2 status in GC tissues, immunohistochemistry and PCR amplification were performed. In silico study was performed for the investigation of interactive potential of HER2 with CagA protein.ResultsPCR amplified the 54 (63.52 %) of 85 GC tissues for HP that showed 34 (62.96 %) cagA+ HP. Immunohistochemistry of tissues revealed 57 (67.05 %) diffuse and 28 (32.94 %) intestinal type cancer. Of 85 cases, 21 GC tissues scored (2 + or 3 +) for positive HER2 expression and score (0 or 1 +) of 64 (75.29 %) showed negative. Of 21 HER2 + GC tissue, 15 biopsies had cagA+ HP and 2 were negative. PCR amplified single amplicon in 17 (20 %) CagA+ tissues and 3 (5.55 %) in CagA - HP. The molecular interactions of CagA was also showed its efficiency for HER2 expression.ConclusionThe study concluded that CagA+ HP may induce HER2 overexpression in GC tissues.

99mTc-HYNIC-(Ser)3-LTVPWY peptide bearing tricine as co-ligand for targeting and imaging of HER2 overexpression tumor

2018 ◽  
Vol 106 (7) ◽  
pp. 601-609 ◽  
Author(s):  
Nazan Aligholikhamseh ◽  
Sajjad Ahmadpour ◽  
Fatemeh Khodadust ◽  
Seyed Mohammad Abedi ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Nude Mice ◽  
Tumor Targeting ◽  
Binding Capacity ◽  
Specific Binding ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Her2 Overexpression ◽  
Her2 Receptor ◽  
Epidermal Growth

Abstract Human epidermal growth factor receptor 2 (HER2) is overexpressed in several cancers. Today’s tumor targeting is receiving more attention due to its specificity to target receptor-dependent cancers. The aim of this study was to evaluate the 99mTc-HYNIC-(tricine)-(Ser)3-LTVPWY peptide for tumor targeting and imaging with overexpression of HER2. HYNIC-(Ser)3-LTVPWY peptide was labeled with 99mTc using tricine as a co-ligand at room temperature. Specific binding of this radiolabeled peptide was assessed on four cancer cell lines with different levels of HER2 receptor expression. Also the affinity of 99mTc-HYNIC-(tricine)-(Ser)3-LTVPWY peptide to the HER2 receptor was evaluated in the SKOV-3 cell line. Biodistribution study of this radiolabeled peptide was performed in SKOV-3 tumor bearing nude mice. The HYNIC conjugated peptide was simply labeled with 99mTc radionuclide with high labeling efficiency about 98±1% showing favorable stability in normal saline and human serum. In the presence of unlabeled peptide as competitor, the HER2 binding capacity of the radiolabeled peptide reduced (approximately five-fold). The KD and Bmax values were found 2.6±0.5 nM and (2.6±0.1)×106, respectively. The tumor/muscle ratios for this radiotracer were determined 1.17±0.77, 1.15±0.32 and 2.65±0.32 at 1, 2 and 4 h after injection, respectively. Presaturation of HER2 receptors in SKOV-3 xenografted nude mice showed a reduction in the tumor/muscle ratio confirming in vivo specificity of the peptide. According to SPECT imaging, the tumor was visualized in mouse after 4 h postinjection of radiolabeled peptide. 99mTc-HYNIC-(tricine)-(Ser)3-LTVPWY peptide exhibited overexpressed HER2 tumor targeting.

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.

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 Current Approaches and Emerging Directions in HER2-resistant Breast Cancer

2014 ◽  
Vol 8 ◽  
pp. BCBCR.S9453 ◽  
Author(s):  
Adam M. Brufsky
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Initial Response ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Intrinsic Resistance ◽  
Her2 Positive

Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab, an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with HER2-positive breast cancer, including improved overall survival in adjuvant and first-line settings. However, a large proportion of patients with breast cancer have intrinsic resistance to HER2-targeted therapies, and nearly all become resistant to therapy after initial response. Elucidation of underlying mechanisms contributing to HER2 resistance has led to development of novel therapeutic strategies, including those targeting HER2 and downstream pathways, heat shock protein 90, telomerase, and vascular endothelial growth factor inhibitors. Numerous clinical trials are ongoing or completed, including phase 3 data for the mammalian target of rapamycin inhibitor everolimus in patients with HER2-resistant breast cancer. This review considers the molecular mechanisms associated with HER2 resistance and evaluates the evidence for use of evolving strategies in patients with HER2-resistant breast cancer.

Immunohistochemical study of p185 HER2 and DF3 in primary breast cancer and correlation with CA-15-3 serum tumor marker

2002 ◽  
Vol 12 (1) ◽  
pp. 74-79
Author(s):  
C Dimas ◽  
M Frangos-Plemenos ◽  
E Kouskouni ◽  
A Kondis-Pafitis
Keyword(s):  
Breast Cancer ◽  
Tumor Marker ◽  
Primary Breast Cancer ◽  
Immunohistochemical Study ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Her2 Overexpression ◽  
Serum Tumor Marker ◽  
Degree Of Differentiation

Abstract.Dimas C, Frangos-Plemenos M, Kouskouni E, Kondis-Pafitis A. Immunohistochemical study of p185 HER2 and DF3 in primary breast cancer and correlation with CA-15-3 serum tumor marker.Human epidermal growth factor receptor 2 (p185 HER2) oncoprotein immunohistochemical expression and DF3 antigen distribution were evaluated in 129 patients with primary breast cancer. p185 HER2 overexpession was positively correlated with the degree of differentiation, metastatic disease, progesterone receptors, and cytoplasmic distribution of DF3 antigen. p185 HER2 overexpression had prognostic significance for the disease-free interval.

scholarly journals Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Nida Iqbal ◽  
Naveed Iqbal
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Therapeutic Implications ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. Dimerization of the receptor results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways leading to cell proliferation and tumorigenesis. Amplification or overexpression of HER2 occurs in approximately 15–30% of breast cancers and 10–30% of gastric/gastroesophageal cancers and serves as a prognostic and predictive biomarker. HER2 overexpression has also been seen in other cancers like ovary, endometrium, bladder, lung, colon, and head and neck. The introduction of HER2 directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers; however, the results have been proved disappointing in other HER2 overexpressing cancers. This review discusses the role of HER2 in various cancers and therapeutic modalities available targeting HER2.

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