scholarly journals The Importance of Epitope Density in Selecting a Sensitive Positive IHC Control

2017 ◽  
Vol 65 (8) ◽  
pp. 463-477 ◽  
Author(s):  
Kodela Vani ◽  
Seshi R. Sompuram ◽  
Anika K. Schaedle ◽  
Anuradha Balasubramanian ◽  
Monika Pilichowska ◽  
...  
Keyword(s):  
Response Curve ◽  
Cell Epitope ◽  
Growth Factor Receptor ◽  
Type Ii ◽  
Analyte Concentration ◽  
Response Range ◽  
Her 2 ◽  
Epidermal Growth ◽  
Epitope Density ◽  
Positive Controls

Clinical Immunohistochemistry (IHC) laboratories face unique challenges in performing accurate and reproducible immunostains. Among these challenges is the use of homemade controls derived from pathological discard samples. Such positive controls have an unknown number of analyte molecules per cell (epitope density). It is unclear how the lack of defined analyte concentrations affects performance of the control. To address this question, we prepared positive IHC controls ( IHControls) for human epidermal growth factor receptor type II (HER-2), estrogen receptor (ER), or progesterone receptor (PR) with well-defined, homogeneous, and reproducible analyte concentrations. Using the IHControls, we examined the effect of analyte concentration on IHC control sensitivity. IHControls and conventional tissue controls were evaluated in a series of simulated primary antibody reagent degradation experiments. The data demonstrate that the ability of a positive IHC control to reveal reagent degradation depends on (1) the analyte concentration in the control and (2) where that concentration falls on the immunostain’s analytic response curve. The most sensitive positive IHC controls have analyte concentrations within or close to the immunostain’s concentration-dependent response range. Strongly staining positive controls having analyte concentrations on the analytic response curve plateau are less sensitive. These findings emphasize the importance of selecting positive IHC controls that are of intermediate (rather than strong) stain intensity.

scholarly journals Advances in targeted therapy for esophageal cancer

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Yan-Ming Yang ◽  
Pan Hong ◽  
Wen Wen Xu ◽  
Qing-Yu He ◽  
Bin Li
Keyword(s):  
Esophageal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Targeted Therapies ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Immune Checkpoints ◽  
Her 2 ◽  
Epidermal Growth

Abstract Esophageal cancer (EC) is one of the most lethal cancers in the world, and its morbidity and mortality rates rank among the top ten in China. Currently, surgical resection, radiotherapy and chemotherapy are the primary clinical treatments for esophageal cancer. However, outcomes are still unsatisfactory due to the limited efficacy and severe adverse effects of conventional treatments. As a new type of approach, targeted therapies have been confirmed to play an important role in the treatment of esophageal cancer; these include cetuximab and bevacizumab, which target epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), respectively. In addition, other drugs targeting surface antigens and signaling pathways or acting on immune checkpoints have been continuously developed. For example, trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), has been approved by the Food and Drug Administration (FDA) as a first-line treatment of HER-2-positive cancer. Moreover, the PD-L1 inhibitor pembrolizumab has been approved as a highly efficient drug for patients with PD-L1-positive or advanced esophageal squamous cell carcinoma (ESCC). These novel drugs can be used alone or in combination with other treatment strategies to further improve the treatment efficacy and prognosis of cancer patients. Nevertheless, adverse events, optimal dosages and effective combinations still need further investigation. In this review, we expound an outline of the latest advances in targeted therapies of esophageal cancer and the mechanisms of relevant drugs, discuss their efficacy and safety, and provide a clinical rationale for precision medicine in esophageal cancer.

scholarly journals Phase I Active Immunotherapy With Combination of Two Chimeric, Human Epidermal Growth Factor Receptor 2, B-Cell Epitopes Fused to a Promiscuous T-Cell Epitope in Patients With Metastatic and/or Recurrent Solid Tumors

2009 ◽  
Vol 27 (31) ◽  
pp. 5270-5277 ◽  
Author(s):  
Pravin T.P. Kaumaya ◽  
Kevin Chu Foy ◽  
Joan Garrett ◽  
Sharad V. Rawale ◽  
Daniele Vicari ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dose Level ◽  
Stable Disease ◽  
Cell Epitope ◽  
Growth Factor Receptor ◽  
T Cell Epitope ◽  
B Cell Epitopes ◽  
Epidermal Growth

Purpose To evaluate the maximum-tolerated dose (MTD), safety profile, and immunogenicity of two chimeric, B-cell epitopes derived from the human epidermal growth factor receptor (HER2) extracellular domain in a combination vaccine with a promiscuous T-cell epitope (ie, MVF) and nor-muramyl-dipeptide as adjuvant emulsified in SEPPIC ISA 720. Patients and Methods Eligible patients with metastatic and/or recurrent solid tumors received three inoculations on days 1, 22, and 43 at doses of total peptide that ranged from 0.5 to 3.0 mg. Immunogenicity was evaluated by enzyme-linked immunosorbent assay, flow cytometry, and HER2 signaling assays. Results Twenty-four patients received three inoculations at the intended dose levels, which elicited antibodies able to recognize native HER2 receptor and inhibited both the proliferation of HER2-expressing cell lines and phosphorylation of the HER2 protein. The MTD was determined to be the highest dose level of 3.0 mg of the combination vaccine. There was a significant increase from dose level 1 (0.5 mg) to dose level 4 (3.0 mg) in HER2-specific antibodies. Four patients (one each with adrenal, colon, ovarian, and squamous cell carcinoma of unknown primary) were judged to have stable disease; two patients (one each with endometrial and ovarian cancer) had partial responses; and 11 patients had progressive disease. Patients with stable disease received 6-month boosts, and one patient received a 20-month boost. Conclusion The combination vaccines were safe and effective in eliciting antibody responses in a subset of patients (62.5%) and were associated with no serious adverse events, autoimmune disease, or cardiotoxicity. There was preliminary evidence of clinical activity in several patients.

scholarly journals Prognostic value of p53, c-ErbB2 and tunel data in upper urothelial carcinoma associated with Balkan nephropathy

2014 ◽  
Vol 66 (2) ◽  
pp. 641-649 ◽  
Author(s):  
Marina Savin ◽  
Z. Dzamic ◽  
M. Baralic ◽  
Sanja Radojevic-Skodric ◽  
Jelena Marinkovic ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Prognostic Value ◽  
Growth Factor Receptor ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Balkan Nephropathy ◽  
Apoptosis Detection ◽  
Environmental Toxin ◽  
Her 2 ◽  
Epidermal Growth

A characteristic tumor suppressor protein 53 (p53) mutational profile of genotoxic action of aristolochic acid was identified in the upper urothelial carcinoma (UUTT) associated with Balkan nephropathy (BEN). In the present study, we examined the prognostic value of tissue-based molecular markers in overall-survival (OS) risk after surgical treatment of UUTT, adjusted for gender, age and urological characteristics in 32 patients with BEN. Immunohistochemical examination of p53, the proliferation cell nuclear antigen (PCNA), the human epidermal growth factor receptor 2 (c-ErbB2; also known as HER-2/neu) proto-oncogene and the in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis detection were used to examine serial tumor sections. The median OS-time was 60 months for UUTT operation; the mortality rate (18.7%) was related to (new) disease (re)occurrence or invasion in 12-216 months. High-grade (p=0.029), TUNEL>0.36%+ cells (p=0.010), and c-ErbB2+ cells (p=0.014) can define the risk of tumor invasion. Patients with Balkan nephropathy that develop UUTT at a stage greater than pT1 (with apoptosis TUNEL+ cells >0.36% and p53+ cells greater than 10%) were at high risk of poor-OS after the tumor surgery (h(x)=6.35; p=0.045). The obtained data present evidence for p53, cErbB2 and apoptosis deregulation, as a result of environmental toxin action. This is the first report of molecular biomarker linkage with OS for BEN-associated UUTT.

TP53 Germline Mutations are Associated with HR+/HER2+ in BRCA1/2-Negative Early-Onset Breast Cancer in China

2022 ◽  
Author(s):  
Lili Chen ◽  
Meng Huang ◽  
Minyan Chen ◽  
Yuxiang Lin ◽  
Jing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
Tp53 Mutation ◽  
Sporadic Breast Cancer ◽  
Molecular Subtype ◽  
Growth Factor Receptor ◽  
Early Onset Breast Cancer ◽  
Her 2 ◽  
Epidermal Growth ◽  
The Relationship

Abstract Background: Except for BRCA1/2, there is no data on the relationship between genetic counseling for the range of mutations and early-onset breast cancer populations. We looked for a link between inherited genes and the molecular subtype of early-onset breast cancer.Methods: We genotyped 1214 individuals with early-onset sporadic breast cancer (age≤40 years) who were BRCA1/2-negative in 3 genes: TP53, PALB2, and RECQL. We focus on the immunohistochemistry characteristics that are unique to each patient. Results: The mutation rates of TP53, PALB2, and RECQL in 1214 BRCA-negative young individuals were 4/1214(0.33%), 8/1214(0.66%), 2/1214(0.16%), respectively. The fact that the TP53 mutation rate was 3.49% among estrogen receptor-and/or progesterone receptor-positive, human epidermal growth factor receptor 2 (HER-2) amplification patients under the age of 35 (P<0.001) was particularly noteworthy. Conclusion: According to the findings, TP53 genetic testing should focus on women under 35 with HR-positive and HER2-positve IDC patients.

HER-2-Amplified Breast Cancer

2018 ◽  
Author(s):  
Zahraa Al-Hilli ◽  
Judy C Boughey
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Aggressive Disease ◽  
Node Positive Disease ◽  
Her 2 ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Amplification of the human epidermal growth factor receptor–2 (HER-2) gene is found in approximately 15 to 30% of breast cancers. Historically, HER-2 overexpression has been associated with aggressive disease and a poor prognosis. However, the use of targeted anti-HER2 therapy has revolutionized the treatment of HER-2-positive disease, and the use of the monoclonal antibody trastuzumab in combination with chemotherapy is now standard of care for tumors greater than 1 cm in size and in node-positive disease. More recently, the value of dual-agent anti-HER-2 therapy has been demonstrated in large clinical trials. This review provides an overview of HER-2-positive breast cancer, its molecular basis, methods of identification, and treatment options and strategies. This review contains 2 figures and 70 references Key words: anti-HER-2 therapy, breast cancer, HER-2-positive breast cancer, HER-2 resistance, lapatinib, neoadjuvant chemotherapy, pertuzumab, small HER-2-positive breast cancer, trastuzumab

Preliminary evaluation of HER-2/neu oncogene and epidermal growth factor receptor expression in normal and neoplastic human ovaries

1992 ◽  
Vol 7 (2) ◽  
pp. 114-118 ◽  
Author(s):  
A.M. Mileo ◽  
M. Fanuele ◽  
F. Battaglia ◽  
G. Scambia ◽  
C. Benedetti-Panici ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Preliminary Evaluation ◽  
Apparent Difference ◽  
Her 2 ◽  
Epidermal Growth ◽  
Neu Oncogene

The HER-2/neu oncogene (a member of the Erb-like oncogene family) is distinct from but closely related to the c-erb B gene which encodes the epidermal growth factor receptor (EGFr). HER-2/neu gene amplification was found in a large number of mammary carcinomas and there was a strong correlation between this phenomenon and poor prognosis. In our study HER-2/neu oncogene expression was determined in 16 malignant ovarian tumors, 2 ovarian lymphomas and 5 normal ovaries. The HER-2/neu gene was found both in normal ovaries and malignant tumors, without any apparent difference among the various histological types. In all the specimens examined, HER-2/neu expression did not seem to be related to EGF binding capacity.

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