scholarly journals Monoclonal Antibodies for Immunohistochemical Diagnosis of Breast Cancer

2021 ◽  
Vol 15 (1) ◽  
pp. 157-163
Author(s):  
Aigerim Turgimbayeva ◽  
Assel Issabekova ◽  
Assylbek Zhylkibayev ◽  
Saule Eskendirova

Breast cancer is a leading malignant disease in women worldwide, although its pathology is visually localised. Currently, it has been proven that the parameters of molecular genetic biomarkers, including oncoprotein HER2, proliferation markers Ki-67, oestrogen receptors ER, and progesterone receptors PgR, are associated with breast carcinogenesis and are a reflection of the biological aggression of the tumour. The significance of these biomarkers in signalling pathways and genetic mechanisms of carcinogenesis has been described, as well as the relationship between the expression levels of each biomarker and the tumour response to appropriate therapy. The primary antibody that imparts specificity to IHC is based on the monoclonal antibodies (mAbs) as the main immunoreagent that enables reliable identification of breast cancer cells. The most commonly used antibodies to molecular biomarkers for IHC were determined in accordance with indicators of laboratory use and efficiency (pass rate) of HER2, Ki-67, ER, PgR assessments in the NordiQC breast cancer module. The discovery of the complete structure of these biomarkers and the design of their domains and subdomains by genetic engineering methods enable the synthesis of effective monoclonal antibodies. Quantitative indicators of the expression levels of tumour biomarkers of breast cancer were determined using mAb, depending on epitope specificity and affinity.

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.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5344 ◽  
Author(s):  
Junnan Wang ◽  
Yiran Wang ◽  
Fei Long ◽  
Fengshang Yan ◽  
Ning Wang ◽  
...  

BackgroundGrowth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) was previously found to be associated with risk of several kinds of human tumors. Here, we studied the expression and clinical significance of GADD45A in breast cancer.MethodsWe performed an immunohistochemical study of GADD45A protein from 419 breast cancer tissues and 116 adjacent non-neoplastic tissues.ResultsSignificantly high GADD45A expression were observed in breast cancer tissues compared with adjacent non-neoplastic tissues (P < 0.001) and were independently correlative with estrogen receptor negative (P = 0.028) and high Ki-67 index (P < 0.001). Kaplan–Meier survival analysis revealed that patients with high GADD45A expression levels had a worse long-term prognosis in triple negative breast cancer (P = 0.041), but it was not an independent prognostic factor in multivariate analysis (P = 0.058).ConclusionsGADD45A expression levels are significantly correlative with estrogen receptor status and Ki-67 index in human breast cancer. Patients with triple negative breast cancer might be stratified into high risk and low risk groups based on the GADD45A expression levels.


2021 ◽  
Vol 11 (5) ◽  
pp. 392-400
Author(s):  
Fajar Lamhot Gultom ◽  
Marliana Nurprilinda ◽  
Ryani Nur Cahyaning Hutami

Immunohistochemistry examination (IHC) is one of the additional tests to diagnose and determine breast cancer subtype. IHC examination is a method to check intracellular protein using a monoclonal and polyclonal antibody to detect the antigen in tissue. IHC examination determined by hormone receptor markers (ER and PR), HER-2/Neu expression, and apoptotic and proliferation markers (Ki-67 and p53) can be used to determine therapy and prognosis. This study aims to determine the hormonal status of breast cancer patient at Siloam Semanggi Hospital in 2018, in the form of age, gender, pathology diagnose, and the result of IHC (ER, PR, HER2, and Ki-67). This study is a retrospective descriptive study using pathological anatomy laboratory results of breast cancer in MRCCC Siloam Semanggi Hospital and 208 patients following inclusion and exclusion criteria. The result obtained is that the age group with the highest frequency is 50-59 years, with 34.1%. The highest frequency by gender is a woman with 99.5%. Carcinoma mammae NST with grade II and III was found in 38.0% of patients. The hormonal receptor with ER and PR positive was found in 51.0% of patients. HER2 expression negative was found in 56.7% of patients. High proliferation Ki-67 was found in 82.7% of patients. Luminal B with HER2 negative subtype was found in 32.2% of patients. Patients in 50-59 years with Luminal B with HER2 negative subtype was found in 26 patients. Patients in carcinoma mammae NST with grade II with Luminal B with HER2 negative subtype was found in 27 patients. Keywords: Breast cancer, pathologic anatomy, immunohistochemistry, breast cancer subtype


Biochemistry ◽  
1987 ◽  
Vol 26 (19) ◽  
pp. 6250-6262 ◽  
Author(s):  
Patricia A. Estes ◽  
Eric J. Suba ◽  
Janet Lawler-Heavner ◽  
Dorraya El-Ashry-Stowers ◽  
Lisa L. Wei ◽  
...  

2020 ◽  
Vol 1 (7) ◽  
pp. 105-107
Author(s):  
Narzieyva D.F ◽  
Jonibekov J.J ◽  
Erkinova Sh.N

Despite significant advances in the early diagnosis and treatment of locally advanced breast cancer, 60–65% of the Republic of Uzbekistan is accounted for by locally advanced breast cancer and its mortality rate is high. The morphological structure of breast cancer is important for the prognosis of the disease. On cell membranes there are special cytoplasmic proteins - receptors, which, when combined with hormones, can affect the rate of division of tumor cells. In terms of the choice of treatment options and the assessment of the forecast, some molecular genetic parameters of the tumor are important, among which, first of all, the hormonal status of the tumor (ER / PR), HER-2 / neu, p53, Bcl-2, Ki-67


2018 ◽  
Vol 14 (3) ◽  
pp. 10-14
Author(s):  
S. M. Demidov ◽  
D. A. Demidov ◽  
S. V. Sazonov ◽  
E. I. Churakova

Objective:an immunohistochemical analysis of the characteristics of a recurrent tumor in breast cancer.Materials and methods.The statistical processing of immunohistochemical analysis’ results was performed and the most frequently encountered molecular-genetic subtypes of breast cancer with the development of local relapses were formulated. The analysis used a standard immunohistochemical panel, which is the “gold standard” for diagnostic in Russia today, and includes the expression of receptors for sex hormones (estrogen and progesterone), expression of the human epidermal growth factor HER2/neu receptor gene, and the index of proliferative activity Ki-67. The 2nd stage of the work was the evaluation of the dynamics of changes in the immunohistochemical characteristics of a recurrent tumor in comparison with the primary one.Results and conclusion.The most common local recurrence provides by triple-negative subtype of breast cancer (42 %). The changes in the immunohistochemical characteristics of a recurrent tumor in comparison with the primary one affected only the index of proliferative activity Ki-67 in the direction of its increase by 12 %.


Author(s):  
M.Kh. Torosyan ◽  
T.V. Shevchenko ◽  
V.V. Rodionov ◽  
Yu.G. Savinov ◽  
Yu.A. Veryaskina ◽  
...  

Luminal HER2-negative breast cancer (BC) detected at early stages is characterized by a relatively favorable course. However, in some cases, there may be a relapse of the disease regardless of the treatment. The aim of the study was to identify predictors of recurrence of primary resectable luminal HER2-negative breast cancer. Materials and Methods. The authors examined biopsies of patients’ breast tumors (n=158) with luminal HER2-negative breast cancer, stage T1-2N0-1M0, as well as anamnestic data of patients. All women were divided into 2 groups: with disease recurrence within the next 5 years after surgery (n=53) and relapse-free patients (n=105). Macroscopic tumor characteristics, its malignancy, total malignancy score, Nottingham prognostic index, Ki-67, expression of receptors for estrogen and progesterone and their influence on relapse were studied. The authors analyzed expression levels of miRNA (miRNA-21, miRNA-221, miRNA-222, miRNA-155, miRNA-205, miRNA-20a, miRNA-125b, miRNA-146b, miRNA-200a) in tumor tissues. Statistical data processing was performed using Statistica 7 (StatSoft Inc., USA) and MedCalc (version 15.2) software. Results. Comparative analysis of miRNA expression levels between groups of patients with recurrent breast cancer (n=21) and relapse-free patients (n=20) revealed a statistically significant increase in the expression levels of miRNA-21, miRNA-205, miRNA-146b, and miRNA-200a in the group with recurrent disease. The authors established the predictive role of the ratios of the expression levels of potentially oncogenic and tumor suppressive miRNA-21/miRNA-155 and miRNA-21/miRNA-205, as well as the role of miRNA-20a in breast cancer recurrence in combination with Ki-67, disease stage, and primary tumor size. Based on the data obtained, they developed a prognostic model to determine the recurrence of primary operable luminal HER2-negative breast cancer. Conclusion. The created prognostic model allows to clearly stratify the prognosis of primary operable luminal HER2-negative breast cancer. Keywords: primary resectable luminal breast cancer without HER2 overexpression, recurrence prognosis, miRNA. Люминальный HER2-негативный рак молочной железы (РМЖ), выявленный на ранних стадиях, характеризуется относительно благоприятным течением. Однако в ряде случаев возникает рецидив заболевания независимо от проведенного лечения. Цель исследования – выявить предикторы рецидивирования первично операбельного люминального HER2-негативного РМЖ. Материалы и методы. Исследовались биоптаты опухолей молочной железы пациенток (n=158) с люминальным HER2-негативным РМЖ стадии T1-2N0-1M0, а также анамнестические данные пациенток. Все женщины были разделены на 2 группы: с рецидивом заболевания в течение последующих 5 лет после проведения операции (n=53) и с безрецидивным течением (n=105). Изучены макроскопические характеристики опухоли, степень злокачественности, суммарный балл злокачественности, Ноттингемский прогностический индекс, Ki-67, экспрессия рецепторов к эстрогену и прогестерону и их влияние на возникновение рецидива. Проведен анализ уровней экспрессии миРНК (миРНК-21, миРНК-221, миРНК-222, миРНК-155, миРНК-205, миРНК-20а, миРНК-125b, миРНК-146b, миРНК-200a) в тканях опухолей. Статистическая обработка данных произведена с помощью программ Statistica 7 (StatSoft Inc., США) и MedCalc (версия 15.2). Результаты. Сравнительный анализ уровней экспрессии миРНК между группами пациенток с рецидивом РМЖ (n=21) и безрецидивным течением (n=20) выявил статистически значимое повышение уровней экспрессии миРНК-21, миРНК-205, миРНК-146b и миРНК-200a в группе с рецидивом заболевания. Установлена предсказывающая роль соотношений уровней экспрессии потенциально онкогенных и онкосупрессорных миРНК-21/миРНК-155 и миРНК-21/миРНК-205, а также роль миРНК-20a в возникновении рецидива РМЖ в сочетании с Кi-67, стадией заболевания, размером первичной опухоли. На основе полученных данных разработана прогностическая модель определения рецидива первично операбельного люминального HER2-негативного РМЖ. Выводы. Созданная прогностическая модель позволяет четко стратифицировать прогноз первично операбельного люминального HER2-негативного РМЖ. Ключевые слова: первично операбельный люминальный рак молочной железы без гиперэкспрессии HER2, прогноз рецидива, миРНК.


2020 ◽  
Vol 10 ◽  
Author(s):  
Yuanhang Yu ◽  
Han Liao ◽  
Rong Xie ◽  
Yue Zhang ◽  
Renjing Zheng ◽  
...  

Triple negative breast cancer (TNBC) is characterized by lack of expression of the estrogen and progesterone receptors and HER2, which are common therapeutic targets. CDK4/6 inhibitor Palbociclib has been approved as an anti-cancer agent for breast cancer. However, identifying biomarkers that predict the response to Palbociclib has always been a challenge for molecular targeted therapy. In this study, we identify microRNA as a hallmark in TNBC patients and explore if miR-3613-3p might serve as a tumor suppressor biomarker for triple negative breast cancer patients and if overexpression of miR-3613-3p could enhance the sensitivity of TNBC cells to Palbociclib. We show that the expression of miR3613-3p was down-regulated in TNBC tumors and cells, and the overexpression of miR-3613-3p in patients’ tumor tissues was clinically and pathologically correlated with favorable prognosis, such as smaller tumor size and the lower Ki-67. In vitro, overexpression of miR-3613-3p inhibited cell proliferation, induced G1 cell-cycle arrest, and enhanced the sensitivity of TNBC cells to Palbociclib treatment. In vivo study revealed that overexpression of miR-3613-3p inhibited TNBC tumorigenesis and exerted a significant inhibitory effect of Palbociclib on MDA-MB-231 cells. Mechanically, SMAD2 and EZH2 were found to be two direct targets of miR-3613-3p and mediate the proliferation of TNBC cells and the sensitivity of the cells to Palbociclib through inducing cellular senescence. Our findings suggested that miR-3613-3p acts as a cancer-suppressor miRNA in TNBC. Moreover, our study showed that miR-3613-3p might be used as a predictive biomarker for the response of TNBC to Palbociclib.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 543-543
Author(s):  
A. M. Gown ◽  
L. C. Goldstein ◽  
P. L. Porter ◽  
R. B. Livingston ◽  
S. Tam ◽  
...  

543 Background: Drugs that poison the mitotic spindle, including taxanes and vinca alkaloids, are active agents against breast cancer. Preliminary evidence showed that high expression levels of tau predicted improved PFS and OS in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim. We now tested whether levels of tau and another microtubule associated protein, beta-tubulin, could predict PFS and OS in multivariate analysis using other prognostic marker studies, including ER, PR, p53 and Ki-67 on a tissue microarray (TMA) obtained from patients in the SWOG S0102 trial. Materials and Methods: Immunohistochemistry (IHC) using antibodies to tau, beta-tubulin, ER, PR, p53, and Ki-67 was performed on a TMA constructed from the S0102 paraffin blocks. All markers were scored semiquantitatively from 0 to 3. Progression free survival (PFS) and overall survival (OS) were evaluated using multivariate analysis. Results: A total of 38 patients (41.3%) were evaluated. Tau was positively correlated with ER (r=0.36; p=0.0325) and PR (r=0.63; p<0.0001), but not with beta tubulin (p=0.34), Ki-67 (p=0.58), or age (p=0.73). Beta tubulin was not significantly correlated with any other markers. Adjusting for age, there was a significant effect of tau expression on OS (HR=0.667, p= 0.0193) and PFS (HR=0.653; p=0.0035), with higher tau associated with longer survival. When adjusted for both age and PR, there was a marginally significant effect of tau on OS (HR=0.582; p=0.056) and PFS (HR=0.604; p= 0.065). Beta tubulin was not associated with OS (HR=0.909; p=0.66) and PFS (HR=0.904; p=0.58) adjusted for age. Conclusions: In multivariate analysis, identification of breast cancer specimens showing high expression levels of tau predicts improved PFS and OS in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim. High expression of tau also correlated with PR and ER expression. These results confirm and expand earlier studies of the predictive power of tau in a multivariate analysis using a panel of IHC markers for breast cancer. No significant financial relationships to disclose.


2021 ◽  
Vol 18 (1) ◽  
pp. 35-42
Author(s):  
E.A. Novikova ◽  
◽  
V.Y. Krokholev ◽  
O.V. Kostromina ◽  
S.M. Demidov ◽  
...  

Aim. In this article, we analyzed the age-related features of molecular- biological subtypes in 499 patients with invasive breast cancer. Materials and research methods. All cases were divided into 5 molecular- biological subtypes based on immunohistochemical studies of hormone receptors, Her2, Ki-67. Luminal (A and B) with the expression of estrogen and/or progesterone receptors (ER+/PR+), accounting for about 50-80% of all breast cancer cases and potentially sensitive, especially luminal A, to hormone therapy. Research results. The analysis showed that in our study the proportion of the Luminal A subtype was lower than the generally accepted values of 37.4% of all studied breast cancer cases. In the group of women under 40 years of age (with preserved menstrual-ovarian function), cases of Luminal A subtype were significantly less common (9.03%) compared to the groups of 41-50 years (p<0.006), 51-60 years (p<0.001), and over 60 (p<0.001). There was also a decrease in the proportion of Luminal A subtype among patients older than 60 years (p=0.0064). No significant differences were found between the groups 41-50 and over 60 years of age (p=0.1868).


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