Ki-67 and Cyclin D1 in subtypes of triple-negative breast cancer with different androgen profiles.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12552-e12552 ◽  
Author(s):  
Larisa N. Vashchenko ◽  
Nikolay S. Karnaukhov ◽  
Tatiana N. Gudtskova ◽  
Mramza V. Kvarchiya ◽  
Elena A. Karnaukhova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cyclin D1 ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Test Results ◽  
Ki 67 ◽  
Cyclin Dependent Kinases ◽  
The Difference ◽  
Student’S T ◽  
High Cyclin

e12552 Background: The purpose of the study was to analyze Ki-67 and Cyclin D1 expression in subtypes of triple negative breast cancer (TNBC) with different androgen profiles. Methods: Tissues of 60 patients with verified TNBC (T1N1M0/T2N0M0, ER-/PR-/Her2-) were studied. Immunohistochemical staining was performed with antibodies to androgen receptors (AR), CK5/6, Ki-67, Cyclin D1, and EGFR. Basal-like (BL) subtype was identified when > 25% cells were CK5/6+ and/or EGFR+ (any staining). Tumors with ≥10% positively stained cells were considered AR+. Parametric statistical methods were used. Significance of the difference between the two means was assessed by the Student's t-test. Results: BL TNBC showed significantly higher Ki-67 expression (81.9±3.1%), compared to other subtypes (70.8±3.1%), p < 0.05. A number of TNBC samples demonstrated Cyclin D1 overexpression ( > 30% stained cells) with no correlation with Ki-67 expression (r = 0.12). High Cyclin D1 levels were less common in BL TNBC (32.4% tumors), compared to other subtypes (43.5% tumors), but its average values were significantly higher (89.9±4.7% vs. 66.5±6.6%, p < 0.05). AR+ tumors were observed in 11 cases (18.3%). Levels of Ki-67 were similar in TNBC with different AR profiles. The percentage of BL tumors was similar in AR+ and AR- cancers (63.6% and 61.3%, respectively). Expression of Cyclin D1 was more frequent in AR+ TNBC (45.5%), vs. 34.7% in АR-. Average levels of Cyclin D1 were significantly higher in AR+ tumors (51.8±13.7%), vs. AR- (31.6±5.1%). Conclusions: TNBC differs in the Cyclin D1 leves; some tumors show its overexpression. Inhibition of cyclin-dependent kinases blocks the cell cycle, which may be useful in the TNBC treatment, which currently has no targets for therapy.

Immunohistochemical evaluation of Cyclin D1 and β-Catenin expression in subtypes of triple-negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12553-e12553
Author(s):  
Tatiana N. Gudtskova ◽  
Larisa N. Vashchenko ◽  
Nikolay S. Karnaukhov ◽  
Mramza V. Kvarchiya ◽  
Ekaterina S. Bosenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cyclin D1 ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Field Of View ◽  
Membrane Expression ◽  
Cytoplasmic Staining ◽  
The Difference ◽  
Student’S T ◽  
High Cyclin

e12553 Background: The purpose of the study was to reveal characteristics of Cyclin D1 and β-Catenin expression in subtypes of triple negative breast cancer (TNBC). Methods: The study included 60 patients diagnosed with verified TNBC (T1N1M0/T2N0M0, ER-/PR-/Her2-). Immunohistochemical staining with CK5/6, EGFR, Cyclin D1, β-Catenin antibodies was performed. Basal-like (BL) subtype was identified when > 25% cells were CK5/6+ and/or EGFR+ (any staining). The expression of β-Catenin was assessed by its location: the membrane, cytoplasm, nucleus. Cells with negative staining on the membrane and cytoplasmic staining were counted and calculated as a percentage of the total number of tumor cells. Nuclear expression of β-Catenin was considered positive with at least 1 positively stained cell in the field of view at x200 magnification. Parametric statistical methods were used. Significance of the difference between the two means was assessed by the Student's t-test. Results: A number of TNBC samples showed Cyclin D1 overexpression. The loss of β-Catenin on the cell membrane and its abnormal accumulation in the cytoplasm was significantly more frequent in TNBC with Cyclin D1 overexpression. These processes were more pronounced in BL cancers. Loss of membrane expression in BL cancers: 29.6±6.1 and 58±7.4%; accumulation in the cytoplasm: 33.4±5.4 and 63.3±7.2%, with low and high Cyclin D1 respectively. Loss of membrane expression in non-BL cancers: 17.6±3.8 and 33.3±4.3%; accumulation in the cytoplasm: 27.3±6.3 and 49.5±8.2%, with low and high Cyclin D1 respectively. Only BL TNBC demonstrated β-catenin translocation to the nucleus (up to 20 stained cells in the field of view): in 33.3% tumors with Cyclin D1 overexpression and in 12% of tumors with its low expression. Conclusions: Levels of expression of β-catenin and Cyclin D1 in TNBC may have predictive value, and the choice of these biomarkers as targets will improve the treatment with new-generation medications.

scholarly journals Immunohistochemical evaluation of Ki-67, Cyclin D1 and β-catenin expression in the subtypes of triple negative breast cancer

2019 ◽  
Vol 100 (2) ◽  
pp. 239-244
Author(s):  
L N Vashchenko ◽  
T N Gudtskova ◽  
E M Nepomnyashchaya ◽  
N S Karnaukhov ◽  
M V Kvarchiya
Keyword(s):  
Breast Cancer ◽  
Cyclin D1 ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Clinical Stage ◽  
Progesterone Receptors ◽  
Ki 67 ◽  
Average Value ◽  
Abnormal Accumulation ◽  
High Level

Aim. To evaluate the expression levels of Ki-67 and cyclin D1 and β-catenin in the subtypes of triple negative breast cancer. Methods. The study was conducted on the surgical material from 60 patients of clinical stage 2A (T1N1M0 or T2N0M0) who were treated at the Rostov Research Institute of Oncology from 2012 to 2015. For immunohistochemistry, antibodies to estrogen and progesterone receptors, cytokeratins 5/6, Ki-67, cyclin D1, β-catenin, HER2/neu and EGFR proteins were used. Results. Triple negative breast cancer with the signs of basal epithelium was found to have a significantly higher expression level of Ki-67 compared to non-basal-like one. In some part of triple negative breast cancer samples overexpression of cyclin D1 was observed. The high level of cyclin D1 in the basal-like subtype was less common than in the subtypes without the signs of basal epithelium, but its average value was significantly higher. In triple negative cancer with cyclin D1 overexpression, the loss of β-catenin on the cell membrane and its abnormal accumulation in the cytoplasm was significantly more frequent. β-catenin translocation into the cell nucleus was observed only in basal-like triple negative cancer, and 2 times more often in case of cyclin D1 overexpression. Conclusion. In triple negative breast cancer tumors with overexpression of cyclin D1 and abnormal expression of β-catenin are observed in some cases; these biomarkers can be considered as potential therapeutic targets for this group of tumors.

scholarly journals TBC1D9: An Important Modulator of Tumorigenesis in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3557
Author(s):  
Charu Kothari ◽  
Alisson Clemenceau ◽  
Geneviève Ouellette ◽  
Kaoutar Ennour-Idrissi ◽  
Annick Michaud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Effective Treatment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Study Analysis ◽  
Tumor Aggressiveness ◽  
Domain Family ◽  
Proliferative Index ◽  
Tumorigenic Potential ◽  
The Difference

Triple-negative breast cancer (TNBC) is a major concern among the different subtypes of breast cancer (BC) due to the lack of effective treatment. In a previous study by our group aimed at understanding the difference between TNBC and non-TNBC tumors, we identified the gene TBC1 domain family member 9 (TBC1D9), the expression of which was lower in TNBC as compared to non-TNBC tumors. In the present study, analysis of TBC1D9 expression in TNBC (n = 58) and non-TNBC (n = 25) patient tumor samples validated that TBC1D9 expression can differentiate TNBC (low) from non-TNBC (high) samples and that expression of TBC1D9 was inversely correlated with grade and proliferative index. Moreover, we found that downregulation of the TBC1D9 gene decreases the proliferation marginally in non-TNBC and was associated with increased migratory and tumorigenic potential in both TNBC and luminal BC cell lines. This increase was mediated by the upregulation of ARL8A, ARL8B, PLK1, HIF1α, STAT3, and SPP1 expression in TBC1D9 knockdown cells. Our results suggest that TBC1D9 expression might limit tumor aggressiveness and that it has a differential expression in TNBC vs. non-TNBC tumors.

scholarly journals Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 416
Author(s):  
Woo Young Sun ◽  
Jina Lee ◽  
Bong Kyun Kim ◽  
Jong Ok Kim ◽  
Joonhong Park
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptor ◽  
Mutation Frequency ◽  
Triple Negative ◽  
Genetic Difference ◽  
Her2 Positive ◽  
Ki 67 ◽  
Hormone Receptor Positive ◽  
Somatic Alteration

This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were PIK3CA, TP53, ERBB2, BRCA2, FANCD2, AKT1, BRCA1, and FANCA. TNBC had significantly lower mutation frequency in PIK3CA (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], p = 0.009), but higher mutation frequency in TP53 (TNBC vs. HRPBC, p = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], p = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC (p = 0.004) due to HRPBC (p < 0.001). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.

scholarly journals Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer

2016 ◽  
Vol 38 (3) ◽  
pp. 1003-1014 ◽  
Author(s):  
Aiyu Zhu ◽  
Yan Li ◽  
Wei Song ◽  
Yumei Xu ◽  
Fang Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative

Background/Aims: Androgen receptor (AR), a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC). However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL) TNBC cells. Methods: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT) or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC) staining after treatment of DHT or bicalutamide. Results: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. Conclusions: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients.

scholarly journals The expression and clinical significance of GADD45A in breast cancer patients

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5344 ◽  
Author(s):  
Junnan Wang ◽  
Yiran Wang ◽  
Fei Long ◽  
Fengshang Yan ◽  
Ning Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Expression Levels ◽  
Cancer Tissues

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.

Demographic variation of Ki67 and its relation with prognosis in triple-negative breast cancer: A single-center pilot project.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11539-e11539
Author(s):  
Mashrafi Ahmed ◽  
Tahmina Begum
Keyword(s):  
Breast Cancer ◽  
Cancer Registry ◽  
Triple Negative Breast Cancer ◽  
Large Scale ◽  
Triple Negative ◽  
Statistical Significance ◽  
Retrospective Chart Review ◽  
Pilot Project ◽  
Single Center ◽  
Ki 67

e11539 Background: Ki-67 is a proliferation marker expressed during cell cycle. ASCO does not recommend this biomarker to be done routinely in breast cancer. As triple negative breast cancer lacks all the ASCO recommended biomarkers (estrogen, progesterone and HER-2 gene), non-recommended markers may carry significant prognostic value in different demographic population. Methods: A retrospective chart review was conducted on patients who were diagnosed with triple negative breast cancer at Saint Joseph Hospital, Chicago from 2005 to 2010. We analyzed the data for Ki67 value among age group, race, menstrual status, tumor histology, stage, treatment given and outcome of the treatment. The data was obtained from medical record, cancer registry and department of pathology. Results: Only 35 cases were found retrospectively. The mean age was 55.6 year. Nearly 47% were African American, 38% White and rest was other races. Most of the cases (71%) were post-menopausal. The average follow-up was 214 days with nearly 62% patients remained disease free, 21% suffered from relapse but alive and 18% died from relapse. The analysis of data is presented here in tabulated form. Conclusions: In our study, we could not reach to statistical significance mostly due to small size of the population. Being a rare subtype of breast cancer, a single center data analysis is not sufficient. This pilot study will encourage us to go for a large scale study involving multi-center or cancer registry data of the state of Illinois. [Table: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text]

Clinicopathologic characteristics of triple-negative breast cancer and relationship to basal markers.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11519-e11519
Author(s):  
Dimitrios Tryfonopoulos ◽  
Georgios Oikonomopoulos ◽  
Stamatina Demiri ◽  
Lazaros Lekakis ◽  
Nikolaos Fragkiskos Pistamaltzian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Stage Iv ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Clinicopathologic Characteristics ◽  
Ki 67 ◽  
Immunohistochemical Markers ◽  
Gene Expression Studies

e11519 Background: Triple negative breast cancers are immunohistochemical surrogates of basal-like breast cancers. There is no complete overlap between triple negative and basal-like tumors and as gene expression studies evolve, further subclassification bearing clinical relevance is underway. Our purpose was to correlate clinicopathologic characteristics of triple negative breast cancer tumors with expression of basal markers in an effort to define immunohistochemically subgroups of this heterogenous disease Methods: Data were retrieved and analysed using our electronic databank. Patient samples were reviewed by an expert breast cancer pathologist and stained additionally for EGFR and CK 5/6 antibodies. Results: Sixty-five women with triple negative breast cancer were identified. Mean age was 58.3±12.9 years. Most tumors (86%) were of ductal histology, 53% grade 3, 48% having high Ki-67 index (>14%). 10% of patients presented with Stage IV, 25% with Stage III, 38% with stage II and 27% with stage I disease. 63% of patients were postmenopausal. EGFR staining was present in 43% of tumor samples, whereas CK 5/6 in 38.5%. Both EGFR and CK 5/6 expression was found in 18.5%, whereas 37% of tumors expressed neither EGFR or CK 5/6. No difference was observed between tumors expressing any of these 2 basal markers as compared to EGFR and CK 5/6 negative tumors in terms of Ki-67 index, grade, tumor size and nodal involvement. Lymphovascular invasion and non-ductal histology tended to occur more frequently (p=ns) in non-basal tumors. Additionally, patients with expression of any of the basal markers tended to be more obese than the non-basal triple negative breast cancer patients (p=ns). Conclusions: Further immunohistochemical markers apart from EGFR and CK 5/6 are needed in order to further define clinically meaningful subgroups of triple negative breast cancer.

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