scholarly journals Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer

2020 ◽  
Author(s):  
Khloud A. Elsharawy ◽  
Maryam Althobiti ◽  
Omar J. Mohammed ◽  
Abrar I. Aljohani ◽  
Michael S. Toss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Molecular Taxonomy ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Nucleolar Protein ◽  
Telomere Maintenance ◽  
Clinicopathological Parameters ◽  
Tumour Grade ◽  
Risk Of Death

Abstract Purpose Nucleolar protein 10 (NOP10) is required for ribosome biogenesis and telomere maintenance and plays a key role in carcinogenesis. This study aims to evaluate the clinical and prognostic significance of NOP10 in breast cancer (BC). Methods NOP10 expression was assessed at mRNA level employing the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1980) and Cancer Genome Atlas (TCGA) BC cohorts (n = 854). Protein expression was evaluated on tissue microarray of a large BC cohort (n = 1081) using immunohistochemistry. The correlation between NOP10 expression, clinicopathological parameters and patient outcome was assessed. Results NOP10 expression was detected in the nucleus and nucleolus of the tumour cells. At the transcriptomic and proteomic levels, NOP10 was significantly associated with aggressive BC features including high tumour grade, high nucleolar score and poor Nottingham Prognostic Index. High NOP10 protein expression was an independent predictor of poor outcome in the whole cohort and in triple-negative BC (TNBC) class (p = 0.002 & p = 0.014, respectively). In chemotherapy- treated patients, high NOP10 protein expression was significantly associated with shorter survival (p = 0.03) and was predictive of higher risk of death (p = 0.028) and development of distant metastasis (p = 0.02) independent of tumour size, nodal stage and tumour grade. Conclusion High NOP10 expression is a poor prognostic biomarker in BC and its expression can help in predicting chemotherapy resistance. Functional assessments are necessary to decipher the underlying mechanisms and to reveal its potential therapeutic values in various BC subtypes especially in the aggressive TNBC class.

scholarly journals RRM2 expression in different molecular subtypes of breast cancer and its prognostic significance

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Manar Ahmed Abdel-Rahman ◽  
Mena Mahfouz ◽  
Hany Onsy Habashy
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tissue Microarrays ◽  
Positive Lymph Node ◽  
Clinicopathological Parameters ◽  
Breast Cancer Patients ◽  
Ribonucleoside Diphosphate Reductase

Abstract Background Breast cancer is one of the most common types of cancer. Ribonucleotide reductase (RNR) is a heterodimeric tetramer consisting of two Ribonucleoside-diphosphate reductase large subunits (RRM1) and two Ribonucleoside-diphosphate reductase small subunits (RRM2). RRM2 is the building subunit of RNR that is important for synthesis of Deoxynucleoside triphosphate (dNTP) during S phase of cell cycle during DNA replication. RRM2 is associated with poor prognosis in lung and colorectal cancer. In breast cancer, increased RRM2 protein level is strongly correlated with large tumour size, positive lymph node and relapse. In this study, we aimed to study expression of RRM2 in breast cancer and to correlate it with different clinicopathological parameters in Egyptian women. Material and methods This study was performed by investigating RRM2 protein expression in breast cancer and correlating the results with other clinicopathological variables using immunohistochemistry and tissue microarrays. Results About 77% of cases were RRM2 positive. High Ki67 was observed in cases with high RRM2 score. The majority of non-luminal cases expressed RRM2, however this was statistically insignificant. In ER positive group, RRM2 expression was associated with shorter disease free survival with borderline significance. Conclusion RRM2 protein expression can help in evaluating outcome of breast cancer patients and could be a potential therapeutic target.

scholarly journals Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer

2021 ◽  
Author(s):  
Maryam Althobiti ◽  
Khloud A. El-sharawy ◽  
Chitra Joseph ◽  
Mohammed Aleskandarany ◽  
Michael S. Toss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Early Stage ◽  
Prognostic Significance ◽  
Tissue Microarrays ◽  
Good Prognosis ◽  
Clinicopathological Parameters ◽  
Luminal Breast Cancer ◽  
Mrna Levels ◽  
Chi Square

Abstract Purpose The outcome of the luminal oestrogen receptor-positive (ER +) subtype of breast cancer (BC) is highly variable and patient stratification needs to be refined. We assessed the prognostic significance of oestrogen-regulated solute carrier family 39 member 6 (SLC39A6) in BC, with emphasis on ER + tumours. Materials and methods SLC39A6 mRNA expression and copy number alterations were assessed using the METABRIC cohort (n = 1980). SLC39A6 protein expression was evaluated in a large (n = 670) and annotated series of early-stage (I–III) operable BC using tissue microarrays and immunohistochemistry. The associations between SLC39A6 expression and clinicopathological parameters, patient outcomes and other ER-related markers were evaluated using Chi-square tests and Kaplan–Meier curves. Results High SLC39A6 mRNA and protein expression was associated with features characteristic of less aggressive tumours in the entire BC cohort and ER + subgroup. SLC39A6 protein expression was detected in the cytoplasm and nuclei of the tumour cells. High SLC39A6 nuclear expression and mRNA levels were positively associated with ER + tumours and expression of ER-related markers, including the progesterone receptor, forkhead box protein A1 and GATA binding protein 3. In the ER + luminal BC, high SLC39A6 expression was independently associated with longer BC-specific survival (BCSS) (P = 0.015, HR 0.678, 95% CI 0.472‒0.972) even in those who did not receive endocrine therapy (P = 0.001, HR 0.701, 95% CI 0.463‒1.062). Conclusion SLC39A6 may be prognostic for a better outcome in ER + luminal BC. Further functional studies to investigate the role of SLC39A6 in ER + luminal BC are warranted.

scholarly journals Prognostic significance of KN motif and ankyrin repeat domains 1 (KANK1) in invasive breast cancer

2019 ◽  
Vol 179 (2) ◽  
pp. 349-357 ◽  
Author(s):  
Yousif A. Kariri ◽  
Chitra Joseph ◽  
Sasagu Kurozumi ◽  
Michael S. Toss ◽  
Mansour Alsaleem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Invasive Breast Cancer ◽  
Tumour Size ◽  
Molecular Taxonomy ◽  
Prognostic Significance ◽  
Ankyrin Repeat ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Cancer Specific Survival

Abstract Background KN motif and ankyrin repeat domains 1 (KANK1) plays an important role in cytoskeleton maintenance and contributes to the regulation of cell proliferation, adhesion and apoptosis. KANK1 is involved in progression of a variety of solid tumours; however, its role in invasive breast cancer (BC) remains unknown. This study aims to evaluate the clinicopathological and prognostic value of KANK1 expression in operable BC. Methods KANK1 expression was assessed at the transcriptomic level using multiple BC cohorts; the Molecular Taxonomy of BC International Consortium cohort (METABRIC; n = 1980), The Cancer Genome Atlas BC cohort (TCGA; n = 949) and the publicly available BC transcriptomic data hosted by BC Gene-Expression Miner (bc-GenExMiner v4.0) and Kaplan–Meier plotter?. The Nottingham BC cohort (n = 1500) prepared as tissue microarrays was used to assess KANK1 protein expression using immunohistochemistry (IHC). The association between clinicopathological variables and patient outcome was investigated. Results In the METABRIC cohort, high expression of KANK1 mRNA was associated with characteristics of good prognosis including lower grade, absence of lymphovascular invasion and HER2 negativity (all; p < 0.001) and with better outcome [p = 0.006, Hazards ratio, (HR) 0.70, 95% CI 0.54–0.91]. High KANK1 protein expression was correlated with smaller tumour size and HER2 negativity, and better outcome in terms of longer breast cancer-specific survival [p = 0.013, HR 0.7, 95% CI 0.536–0.893] and time to distant metastasis [p = 0.033, HR 0.65, 95% CI 0.51–0.819]. Conclusion These results supported that upregulation of KANK1 works as a tumour suppressor gene in BC and is associated with improved patients’ outcomes.

scholarly journals Prognostic Significance of Microvessel Density as Assessed by anti CD34 Monoclonal Antibody in Invasive Ductal Carcinoma of Breast

2020 ◽  
Vol 5 (3) ◽  
pp. 75-79
Author(s):  
Bhawna Agnani ◽  
Ranjana Solanki ◽  
Maryem Ansari ◽  
Sankalp Agnani
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Microvessel Density ◽  
Tumor Size ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Histologic Grade ◽  
Histological Evaluation ◽  
Clinicopathological Parameters ◽  
Lymph Node Status

Context and Aim: Breast carcinoma is one of the leading causes of cancer related mortality in females. A number of established prognostic indicators exist for breast cancer. One potential indicator of adverse prognosis in breast cancer is tumor induced angiogenesis. Hematogenous spread of tumor cells is quantitatively related to microvessel density (MVD). This study aims to find possible association of microvessel density with other recognized prognostic factor such as patient age, tumor size, lymph node status, histologic grade, Nottingham Prognostic Index (NPI), vascular invasion, hormone receptor status and HER2/Neu expression in breast carcinoma.Methods and Materials: This is a cross sectional, laboratory based descriptive type of observational study. This study was carried out in the Department of Pathology, SMS medical college. In our study we did histological evaluation of mastectomy specimen of breast cancer including ER, PR and Her 2 status and calculated the microvessel density (MVD) in appropriate section by applying IHC. MVD correlation with other clinicopathological parameters was done. Stastical analysis used in this study include Fischer Exact test and Chi Square test. Results: A significant correlation was obtained between MVD and tumor size, lymph node metastasis, lymphovascular invasion, histologic grade and NPI (P value of 0.01). Conclusions: Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. The correlation of MVD with prognosis suggests the utility of antiangiogenic drugs in breast cancer patients with high angiogenesis

scholarly journals The prognostic significance of wild-type isocitrate dehydrogenase 2 (IDH2) in breast cancer

2019 ◽  
Vol 179 (1) ◽  
pp. 79-90 ◽  
Author(s):  
Abrar I. Aljohani ◽  
Michael S. Toss ◽  
Sasagu Kurozumi ◽  
Chitra Joseph ◽  
Mohammed A. Aleskandarany ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Isocitrate Dehydrogenase ◽  
Ductal Carcinoma ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Wild Type ◽  
Hormonal Receptor ◽  
Isocitrate Dehydrogenase 2 ◽  
Receptor Negativity

Abstract Background Lymphovascular invasion (LVI) is a prerequisite step in breast cancer (BC) metastasis. We have previously identified wild-type isocitrate dehydrogenase 2 (IDH2) as a key putative driver of LVI. Thus, we explored the prognostic significance of IDH2 at transcriptome and protein expression levels in pre-invasive and invasive disease. Methods Utlising tissue microarrays from a large well annotated BC cohort including ductal carcinoma in situ and invasive breast cancer (IBC), IDH2 was assessed at the transcriptomic and proteomic level. The associations between clinicopathological factors including LVI status, prognosis and the expression of IDH2 were evaluated. Results In pure DCIS and IBC, high IDH2 protein expression was associated with features of aggressiveness including high nuclear grade, larger size, comedo necrosis and hormonal receptor negativity and LVI, higher grade, larger tumour size, high NPI, HER2 positivity, and hormonal receptor negativity, respectively. High expression of IDH2 either in mRNA or in protein levels was associated with poor patient’s outcome in both DCIS and IBC. Multivariate analysis revealed that IDH2 protein expression was an independent risk factor for shorter BC specific-survival. Conclusion Further functional studies to decipher the role of IDH2 and its mechanism of action as a driver of BC progression and LVI are warranted.

PR149 PROGNOSTIC SIGNIFICANCE OF KI67 PROTEIN EXPRESSION IN METASTATIC BREAST CANCER SURVIVAL

The Breast ◽  
2015 ◽  
Vol 24 ◽  
pp. S73
Author(s):  
Natasa Todorovic-Rakovic ◽  
Ksenija Kanjer ◽  
Zora Neskovic-Konstantinovic
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Protein Expression ◽  
Cancer Survival ◽  
Prognostic Significance ◽  
Metastatic Breast ◽  
Breast Cancer Survival

scholarly journals PROGNOSTIC VALUE OF EXPRESSION OF ANDROGENETIC RECEPTORS IN DIFFERENT MOLECULAR TYPES OF BREAST CANCER

2017 ◽  
Vol 16 (1) ◽  
pp. 32-37
Author(s):  
D. A. Ryabchikov ◽  
I. K. Vorotnikov ◽  
N. A. Kozlov ◽  
N. V. Chkhikvadze ◽  
K. S. Titov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Value ◽  
Tumor Tissue ◽  
Molecular Subtypes ◽  
Biological Fluids ◽  
Prognostic Significance ◽  
Immunohistochemical Expression ◽  
Risk Of Death ◽  
The Relationship ◽  
Positive Breast Cancer

Introduction. So far in the literature there is no consensus on the relationship between the level of androgens and their metabolites in various biological fluids and tissues with the development of breast cancer. As suggested by many researchers, determining the level of androgenetic receptors (AR) in the tumor in patients with breast cancer are able to access a number of promising directions in the study of prognosis of the disease and the search for new approaches to endocrine therapy of different molecular subtypes of breast cancer. Objective. To evaluate the clinical and prognostic significance of the immunohistochemical expression of AR in different molecular types of breast cancer. Materials and methods. In the present work we have studied the expression of AR in tumor tissue in patients of different molecular types of breast cancer. Results. The risk of death in patients with AR-positive breast cancer is 88 % lower than in patients with AR-negative tumors. Conclusion. It was concluded that the study of the expression of AR, is a promising direction not only in the assessment of the prognosis of the disease, but when searching for additional approaches to the treatment of breast cancer.

scholarly journals Prognostic significance of PD-L1-positive cancer-associated fibroblasts in patients with triple-negative breast cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Katsuhiro Yoshikawa ◽  
Mitsuaki Ishida ◽  
Hirotsugu Yanai ◽  
Koji Tsuta ◽  
Mitsugu Sekimoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Tissue Microarrays ◽  
Tumour Microenvironment ◽  
Clinicopathological Parameters ◽  
Cancer Associated Fibroblasts ◽  
Clinicopathological Significance

Abstract Background Cancer-associated fibroblasts (CAFs) are some of the most abundant components of the tumour microenvironment. A recent study suggested that in some cancers, CAFs express programmed death ligand 1 (PD-L1), which can act as a prognostic marker. The aim of this study was to investigate the clinicopathological significance of CAF PD-L1 expression in patients with triple-negative breast cancer (TNBC) and to identify the most suitable primary antibody for immunostaining for CAF PD-L1. Methods Immunohistochemical staining (primary antibodies of 73–10, SP142, and E1L3N) and tissue microarrays were used to analyse the expression profiles of PD-L1 in CAF in 61 patients with TNBC who underwent surgery. Overall survival (OS) was compared based on CAF PD-L1 expression, and the risk factors for OS were analysed. The relationship between clinicopathological parameters and survival was also examined. Results Thirty-four (55.7%) patients were positive for CAF PD-L1 (73–10) expression. Compared with CAF PD-L1 negativity, there was a significant correlation between CAF PD-L1 positivity and better OS (p = 0.029). CAF PD-L1 expression, evaluated using SP-142 or E1L3N, did not correlate with OS. CAF PD-L1-positivity (73–10) correlated significantly with better prognosis in multivariate analyses (hazard ratio: 0.198; 95% confidence interval: 0.044–0.891; p = 0.035). Conclusions CAF PD-L1 expression is a novel marker for a better prognosis of patients with TNBC, and the 73–10 assay may be suitable for immunostaining CAF PD-L1.

scholarly journals Bioinformatics analysis revealing prognostic significance of RRM2 gene in breast cancer

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Wei-xian Chen ◽  
Liang-gen Yang ◽  
Ling-yun Xu ◽  
Lin Cheng ◽  
Qi Qian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Bioinformatics Analysis ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
Cancer Prognosis ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Metastatic Relapse

Abstract Background: Ribonucleotide reductase M2 subunit (RRM2) plays vital roles in many cellular processes such as cell proliferation, invasiveness, migration, angiogenesis, senescence, and tumorigenesis. However, the prognostic significance of RRM2 gene in breast cancer remains to be investigated. Methods:RRM2 expression was initially evaluated using the Oncomine database. The relevance between RRM2 level and clinical parameters as well as survival data in breast cancer was analyzed using the Kaplan–Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases. Results:RRM2 was overexpressed in different subtypes of breast cancer patients. Estrogen receptor (ER) and progesterone receptor (PR) were negatively correlated with RRM2 expression. Conversely, the Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), human epidermal growth factor receptor-2 (HER-2) status, nodal status, basal-like status, and triple-negative status were positively related to RRM2 level in breast cancer samples with respect to normal tissues. Patients with increased RRM2 showed worse overall survival, relapse-free survival, distant metastasis-free survival, disease-specific survival, and disease-free survival. RRM2 also exerted positive effect on metastatic relapse event. Besides, a positive correlation between RRM2 and KIF11 genes was confirmed. Conclusion: Bioinformatics analysis revealed that RRM2 might be used as a predictive biomarker for prognosis of breast cancer. Further studies are needed to more precisely elucidate the value of RRM2 in evaluating breast cancer prognosis.

Distribution and prognostic significance of cell cycle proteins in squamous carcinoma of the larynx, hypopharynx and adjacent epithelial hyperplastic lesions

2003 ◽  
Vol 117 (4) ◽  
pp. 286-293 ◽  
Author(s):  
Metka Volavšek ◽  
Matej Bračko ◽  
Nina Gale
Keyword(s):  
Cell Cycle ◽  
Protein Expression ◽  
Cyclin D1 ◽  
Prognostic Significance ◽  
Squamous Carcinoma ◽  
Malignant Tumours ◽  
Tumour Grade ◽  
Cancer Specific Survival ◽  
Biological Behaviour ◽  
Cell Cycle Proteins

Alterations of cell cycle proteins contribute to the development and biological behaviour of malignant tumours. We evaluated the distribution and prognostic significance of immunohistochemically detected proteins p53, p21, Rb, and cyclin D1 in 101 laryngeal and hypopharyngeal squamous cell carcinomas (SCC) and adjacent epithelial hyperplastic lesions (EHL). Protein expression was correlated with tumour grade and stage.Varying patterns of protein expression were found in SCC. A significant correlation (p <0.05) was found between Rb expression and tumour grade. Different grades of EHL exhibited randomly distributed p53 and cyclin D1 positive cell clusters with no association to the pattern of their expression in SCC.Our study demonstrated derailment of cell cycle regulation in almost all cases of SCC of the larynx and hypopharynx. However, only cyclin D1 expression had an independent prognostic value for cancer-specific survival. The results also suggest that Rb gene inactivation, although rare, might be more important in the development of SCC than previously thought.

Sign in / Sign up

Export Citation Format

Share Document