Heterogeneity vs. Asynchrony of Receptor Expression in Breast Cancer as Determined by Monoclonal Antibodies

Author(s):  
L. B. Kinsel ◽  
J. L. Flowers ◽  
J. Konrath ◽  
G. S. Leight ◽  
G. L. Greene ◽  
...  
2021 ◽  
Author(s):  
Gilda Schmidt ◽  
Margit Maria Guhl ◽  
Erich-Franz Solomayer ◽  
Gudrun Wagenpfeil ◽  
Mohammed Eid Hammadeh ◽  
...  

Abstract Background: PD-L1 receptor expression in breast cancer tissue can be assessed with different anti-human PD-L1 monoclonal antibodies. The performance of three specific monoclonal antibodies in a head-to-head comparison is unknown. Also, a potential correlation of PD-L1 expression and clinico-pathological parameters has not been investigated.MethodsThis was a retrospective study on tissue samples of patients with histologically confirmed triple negative breast cancer (TNBC). PD-L1 receptors were immune histochemically stained with three anti-human PD-L1 monoclonal antibodies: 22C3 and 28-8 for staining of tumor cell membranes (TC) and cytoplasm (Cyt), SP142 for immune cell staining (IC).Three different tissue samples of each patient were evaluated separately by two observers in a blinded fashion. The percentage of PD-L1 positive tumor cells in relation to the total number of tumor cells was determined. For antibodies 22C3 and 28-8 PD-L1 staining of 0 to <1% of tumor cells was rated "negative", 1 to 50% was rated "positive" and > 50% was rated "strong positive". Cyt staining was defined as “negative” when no signal was observed and as “positive”, when any positive signal was observed. For IC staining with SP142 all samples with PD-L1 expression ≥1% were rated as “positive”. Finally, the relationship between PD-L1 expression and clinico-pathological parameters was analyzed.Results Tissue samples from 59 of 60 enrolled patients could be analyzed. Mean age was 55 years. Both the monoclonal antibodies 22C3 and 28-8 had similar properties, and were positive for both TC in 13 patients (22%) and for Cyt staining in 24 patients (40.7%). IC staining with antibody SP142 was positive in 24 patients (40.7%), who were also positive for Cyt staining. The differences between TC and Cyt staining and TC and IC staining were significant (p=0.001). Cases with positive TC staining showed higher Ki67 expression compared to those with negative staining, 40% vs 30%, respectively (p=0.05). None of the other clinico-pathological parameters showed any correlation with PDL1 expression. ConclusionAntibodies 22C3 and 28-8 can be used interchangeably for PD-L1 determination in tumor cells of TNBC patients. Results for Cyt staining with 22C3 or 28-8 and IC staining with SP142 were identical. PD-L1 expression correlates with Ki67 expression but not with OS or DFS.


Maturitas ◽  
2012 ◽  
Vol 71 ◽  
pp. S32-S33
Author(s):  
K.P. Madeira ◽  
R.D. Daltoe ◽  
G.M. Sirtoli ◽  
L.C.D. Rezende ◽  
A. Assis ◽  
...  

Author(s):  
Mukkamala Durga Niharika ◽  
Shaik Kulsumbi ◽  
Devagiri Anupama ◽  
Tadigiri Vineela Supriya ◽  
Kotari Navya ◽  
...  

Cancer is a life-threatening disease which causes to lose cohesiveness and orderliness of normal tissue. These malignant cells can spread to any other organ through blood flow or lymphatic flow and develop malignancy over there; this phenomenon is called metastasis. The aim is to focus on treatment pattern and response of drugs in various stages of breast cancer along with epidemiology. It is a non- interventional multicentric observational study. Female patients confirmed with Breast cancer are included in the study. All the relevant data were collected on a patient demographic form after obtaining informed consent from individual patients. In our study, the mean age of presentation in breast cancer patients was 41.35 years. Further it was found that 40.5% (n = 81) majority-female patients with Breast cancer are from Guntur District and 21.5% (n= 43). The majority of women with Breast cancer have hormone receptor expression of ER+/PR+HER2- was found to be 33% (n= 50). In the study on analyzing comorbidities of the study population, it was noted that 28.5% of women were affected with Diabetes mellitus. In our study, it was found that most of the patients with Breast cancer have been most often prescribed with Adriamycin 27.86%. From these observations, we conclude that late menarche may be one of the etiological causes of breast cancer in women, Invasive carcinoma in situ is the most commonly reported breast cancer in the study. Patients have been diagnosed with breast cancer at their stage 3 of progression, which may be the reason for making it mandatory for more than 50% of patients to undergo 6 to 8 cycles of chemotherapy. Coming to the patterns of drug use, ADRIAMYCIN, CYCLOPHOSPHAMIDE and DOCETAXEL are the three most commonly used single drug and combinational drug therapies among the study population.


2008 ◽  
Vol 47 (04) ◽  
pp. 322-327 ◽  
Author(s):  
D. Blokh ◽  
N. Zurgil ◽  
I. Stambler ◽  
E. Afrimzon ◽  
Y. Shafran ◽  
...  

Summary Objectives: Formal diagnostic modeling is an important line of modern biological and medical research. The construction of a formal diagnostic model consists of two stages: first, the estimation of correlation between model parameters and the disease under consideration; and second, the construction of a diagnostic decision rule using these correlation estimates. A serious drawback of current diagnostic models is the absence of a unified mathematical methodological approach to implementing these two stages. The absence of aunified approach makesthe theoretical/biomedical substantiation of diagnostic rules difficult and reduces the efficacyofactual diagnostic model application. Methods: The present study constructs a formal model for breast cancer detection. The diagnostic model is based on information theory. Normalized mutual information is chosen as the measure of relevance between parameters and the patterns studied. The “nearest neighbor” rule is utilized for diagnosis, while the distance between elements is the weighted Hamming distance. The model concomitantly employs cellular fluorescence polarization as the quantitative input parameter and cell receptor expression as qualitative parameters. Results: Twenty-four healthy individuals and 34 patients (not including the subjects analyzed for the model construction) were tested by the model. Twenty-three healthy subjects and 34 patients were correctly diagnosed. Conclusions: The proposed diagnostic model is an open one,i.e.it can accommodate new additional parameters, which may increase its effectiveness.


2020 ◽  
Vol 21 (11) ◽  
pp. 1097-1102
Author(s):  
Drashti Desai ◽  
Pravin Shende

: Immunotherapy emerges as a treatment strategy for breast cancer marker, diagnosis and treatment. In this review, monoclonal antibodies (mAbs)-based passive and peptide vaccines as active immunotherapy approaches like activation of B-cells and T-cells are studied. Passive immunotherapy is mAbs-based therapy effective against tumor cells, which acts by targeting HER2, IGF 1R, VEGF, BCSC and immune checkpoints. Neuropeptide Y (NPY) and GPCR are the areas of interest to target BC metastases for on-targeting therapeutic action. Neuropeptide S (NPS) or NPS receptor 1, acts as a biomarker for Neuroendocrine tumors (NET), mostly characterized by synaptophysin and chromogranin-A expression or Ki-67 proliferation index. The protein fusion technologies arise as a promising avenue in plant expression systems for increased recombinant Ab accumulation and cost-efficient purification. Recently, mAbs-based immunotherapy effectiveness is appreciated as a novel therapeutic combination of chemotherapy and immunotherapy to reduce the side effects and improve therapeutic responsiveness. Synthetic drug resistance will be overcome by mAbs-based therapy through several clinical trials and detection methods need to be optimized for accuracy and precision. Pharmacokinetic attributes need to be accessed for preferred receptor-agonist activity without ligand accumulation.


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