scholarly journals Comparison of Clinicopathological Characteristics of BRCA1 and BRCA2 Carriers with Breast Cancer: The Role of Ki-67 Index

2021 ◽  
Vol 7 (3) ◽  
pp. 91-97
Author(s):  
Recep AK ◽  
Cengiz KARAÇİN ◽  
Taha BAHSİ ◽  
Ömür Berna ÖKSÜZOĞLU
Keyword(s):  
Breast Cancer ◽  
Clinicopathological Characteristics ◽  
Brca1 And Brca2 ◽  
Ki 67

scholarly journals Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jun-Xian Du ◽  
Yi-Hong Luo ◽  
Si-Jia Zhang ◽  
Biao Wang ◽  
Cong Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
High Risk Group ◽  
Clinical Samples ◽  
Binding Motif ◽  
Ki 67 ◽  
Tissue Samples

Abstract Background Intensive evidence has highlighted the effect of aberrant alternative splicing (AS) events on cancer progression when triggered by dysregulation of the SR protein family. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA. Methods We conducted a comprehensive analysis of the expression and clinical correlation of SRSF1 in BRCA based on the TCGA dataset, Metabric database and clinical tissue samples. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and their binding motifs were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. PTPMT1 exon 3 (E3) AS was identified to partially mediate the oncogenic role of SRSF1 by the P-AKT/C-MYC axis. Finally, the expression and clinical significance of these AS events were validated in clinical samples and using the TCGA database. Results SRSF1 expression was consistently upregulated in BRCA samples, positively associated with tumor grade and the Ki-67 index, and correlated with poor prognosis in a hormone receptor-positive (HR+) cohort, which facilitated proliferation, cell migration and inhibited apoptosis in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of splice switching of PTPMT1. Furthermore, PTPMT1 splice switching was regulated by SRSF1 by binding directly to its motif in E3 which partially mediated the oncogenic role of SRSF1 by the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients and using the TCGA database. The high-risk group, identified by AS of PTPMT1 and expression of SRSF1, possessed poorer prognosis in the stage I/II TCGA BRCA cohort. Conclusions SRSF1 exerts oncogenic roles in BRCA partially by regulating the AS of PTPMT1, which could be a therapeutic target candidate in BRCA and a prognostic factor in HR+ BRCA patient.

scholarly journals The Mammary Gland Carcinogens: The Role of Metal Compounds and Organic Solvents

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Stephen Juma Mulware
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Organic Solvents ◽  
Redox Regulation ◽  
Dna Hypermethylation ◽  
Brca1 And Brca2 ◽  
Metal Compounds ◽  
Breast Physiology ◽  
Fat Depot

The increased rate of breast cancer incidences especially among postmenopausal women has been reported in recent decades. Despite the fact that women who inherited mutations in the BRCA1 and BRCA2 genes have a high risk of developing breast cancer, studies have also shown that significant exposure to certain metal compounds and organic solvents also increases the risks of mammary gland carcinogenesis. While physiological properties govern the uptake, intracellular distribution, and binding of metal compounds, their interaction with proteins seems to be the most relevant process for metal carcinogenicity than biding to DNA. The four most predominant mechanisms for metal carcinogenicity include (1) interference with cellular redox regulation and induction of oxidative stress, (2) inhibition of major DNA repair, (3) deregulation of cell proliferation, and (4) epigenetic inactivation of genes by DNA hypermethylation. On the other hand, most organic solvents are highly lipophilic and are biotransformed mainly in the liver and the kidney through a series of oxidative and reductive reactions, some of which result in bioactivation. The breast physiology, notably the parenchyma, is embedded in a fat depot capable of storing lipophilic xenobiotics. This paper reviews the role of metal compounds and organic solvents in breast cancer development.

scholarly journals The Analysis of bcl-2 in Association with p53 and Ki-67 in Triple Negative Breast Cancer and Other Molecular Subtypes in Ghana

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Charity Ameh-Mensah ◽  
Babatunde Moses Duduyemi ◽  
Kweku Bedu-Addo ◽  
Elijah Atta Manu ◽  
Francis Opoku ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Histological Grade ◽  
Her2 Overexpression ◽  
Luminal A ◽  
Ki 67 ◽  
Cross Sectional ◽  
Luminal B ◽  
Protein P53

Background. Little is known about the role of apoptosis in the tumorigenesis and prognosis of breast cancer in Ghana. Chemotherapeutic drug efficacy partially relates to apoptosis induction, rendering it a vital target in cancer therapy with unique biomarker opportunities that have not been exploited. Aberrations in this pathway are central to tumorigenesis, tumor progression, overall tumor growth, and regression during treatment therapies. Antiapoptotic bcl-2 (gene) and p53 are known to play roles in apoptosis while Ki-67 is a proliferative marker. The aim of our study is to determine the association of bcl-2 (protein) with p53 and Ki-67 in 203 consecutive breast cancer cases over a 10-year period. Method. A retrospective cross-sectional study on archival FFPE tissue blocks over a 9-year period with abstraction of clinicopathologic data. Two hundred and three consecutive and suitable FFPE blocks were selected for tissue microarray (TMA) construction, and IHC (bcl-2 (protein), Ki-67, p53, cyclin D, pan cytokeratins A and E, ER, PR, and HER2/neu) was done. Expressions of bcl-2 (protein), p53, and Ki-67 were related to histological grade, lymphovascular invasion, and molecular subtypes. SPSS version 23 was used to analyze results. Results. Most of our cases were in the fifth decade of life (31%); invasive carcinoma of no special type (NST) was predominant (87%); histological grade III (38%) was the highest; and Luminal A (19.8%), Luminal B (9.9%), HER2 (16%), and TNBC (54.3%) constituted the molecular classes. bcl-2 expression was found in 38% of the cases. Our cases also showed mutation in p53 (36.7%) and ki-67 expression (62.5%). bcl-2 (protein) and p53 significantly correlated with Luminal B and TNBC ( p < 0.01 ). Ki-67 also correlated significantly with Luminal A and B and HER2 overexpression ( p < 0.01 ). Premenopausal age (40–49) and histological grade inversely correlated with bcl-2 (protein) expression. p53 statistically correlated with Ki-67 ( p < 0.05 ). Conclusion. Our results show high expression of bcl-2 (protein) suggesting an important role of apoptosis in Ghanaian breast cancer cases. bcl-2 (protein), p53, and Ki-67 expressions emerged interdependently from this research and can thus be manipulated in prediction and prognosis of breast cancers in our setting.

scholarly journals PREDICTIVE RELAPSE MODEL IN PATIENTS WITH LUMINAL HER2-NEGATIVE BREAST CANCER

2020 ◽  
pp. 61-73
Author(s):  
M.Kh. Torosyan ◽  
T.V. Shevchenko ◽  
V.V. Rodionov ◽  
Yu.G. Savinov ◽  
Yu.A. Veryaskina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Model ◽  
Prognostic Index ◽  
Cancer Recurrence ◽  
Disease Stage ◽  
Luminal Breast Cancer ◽  
Her2 Overexpression ◽  
Ki 67 ◽  
Expression Levels

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.

scholarly journals Androgen Receptor Expression Associates With Distinctive Clinicopathological and Molecular Features in ER-Positive and ER-Negative Breast Cancer

2021 ◽  
Author(s):  
Taobo Hu ◽  
Yiqiang Liu ◽  
Guiyang Zhao ◽  
Shu Wang ◽  
Mengping Long
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Clinicopathological Characteristics ◽  
Receptor Expression ◽  
Molecular Features ◽  
Molecular Correlation ◽  
Er Positive ◽  
Er Expression ◽  
Positive Breast Cancer

Abstract Background: Androgen receptor (AR) expression is frequently observed in breast cancer, but its association with estrogen receptor (ER) expression of breast cancer remains unclear. Methods: In this study, we analyzed the clinicopathological and molecular features associated AR loss in ER-positive and ER-negative breast cancer respectively, trying to elucidate the molecular correlation between AR and ER. Results: Our results showed that AR loss was associated with different clinicopathological characteristics in ER-positive and ER-negative breast cancer. Moreover, the expression of AR was correlated with different molecular features in ER-positive and ER-negative breast cancer.Conclusions: These results suggest that the role of AR in ER-positive breast cancer is distinctive from that in ER-negative breast cancer.

Role of breast surgery in T1-T3 breast cancer patients with synchronous bone metastases.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1115-1115 ◽  
Author(s):  
Edoardo Botteri ◽  
Elisabetta Munzone ◽  
Vincenzo Bagnardi ◽  
Mattia Intra ◽  
Nicole Rotmensz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Bone Metastases ◽  
Breast Surgery ◽  
Treatment Strategies ◽  
Surgical Margins ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Ki 67

1115 Background: The role of breast surgery in advanced breast cancer (ABC) is controversial. The main potential advantage of removing the primary tumor is to eliminate the source of further metastatic spread. While previous studies addressed the question in very heterogeneous populations (e.g. patients with any local and distant extension), we have focused on a homogeneous series of ABC patients. Methods: From our institutional Tumor Registry we selected 191 consecutive women diagnosed between 2000 and 2008 with locally operable (T1-T3) ABC, synchronous bone metastases and no other distant sites involved. The progression free survival (PFS) was calculated from diagnosis to the date of progression, defined as either a new site of metastatic disease or clinical/radiographic evidence of increasing tumor burden at a previously known bone metastatic site. Results: Median age was 51 years and 92% of the women had an endocrine-responsive tumor. One-hundred and thirty patients out of 191 (68%) underwent surgery at the time of diagnosis, while 61 (32%) did not. Twenty-six of the operated patients (20%) had previously undergone neoadjuvant chemotherapy; 15 (12%) had positive or undetermined surgical margins. Operated and non-operated patients were similar with respect to age, tumor size, nodal involvement, estrogen and progesterone receptor status, HER2 overexpression and Ki-67, but differed in terms of number of bone metastatic sites: a single metastasis was detected in 34 (26%) operated and 7 (11%) non-operated cases (P=0.02). First-line treatment strategies with endocrine therapy, chemotherapy and Trastuzumab were similarly distributed between the two groups. The 5-year PFS was 22.0% and 10.4% in operated and non-operated patients, respectively. The multi-adjusted hazard ratio was 0.62 (95% confidence interval 0.39-0.98) in favor of surgery. The exclusion of the patients who had received neoadjuvant chemotherapy and patients with positive or undetermined surgical margins did not alter the results. Conclusions: In this large and homogeneous series of ABC patients with synchronous bone metastases, the role of breast surgery had a favorable impact on the progression of the disease, indicating a potential survival benefit.

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