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.

scholarly journals The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3963
Author(s):  
Brendah K. Masisi ◽  
Rokaya El Ansari ◽  
Lutfi Alfarsi ◽  
Madeleine L. Craze ◽  
Natasha Jewa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Patient Outcome ◽  
Ductal Carcinoma ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Glutamine Metabolism ◽  
Gene Copy ◽  
Luminal Breast Cancer ◽  
Potential Biomarker

The glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assessed at genomic/transcriptomic levels, using METABRIC (n = 1398) and GeneMiner datasets (n = 4712), and protein using immunohistochemistry in well-characterised cohorts of Oestrogen receptor-positive/HER2-negative BC patients: ductal carcinoma in situ (DCIS; n = 206) and invasive breast cancer (IBC; n = 717). Glutaminase expression was associated with clinicopathological features, patient outcome and glutamine-metabolism-related genes. In DCIS, GLS alone and GLS+/GLS2- expression were risk factors for shorter local recurrence-free interval (p < 0.0001 and p = 0.001, respectively) and remained prognostic factors independent of tumour size, grade and comedo necrosis (p = 0.0008 and p = 0.003, respectively). In IBC, GLS gene copy number gain with high mRNA expression was associated with poor patient outcome (p = 0.011), whereas high GLS2 protein was predictive of a longer disease-free survival (p = 0.006). Glutaminase plays a role in the biological function of luminal BC, particularly GLS in the early non-invasive stage, which could be used as a potential biomarker to predict disease progression and a target for inhibition. Further validation is required to confirm these observations, and functional assessments are needed to explore their specific roles.

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 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 Ki67 index in intrinsic breast cancer subtypes and its association with prognostic parameters

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Atif Ali Hashmi ◽  
Kashif Ali Hashmi ◽  
Muhammad Irfan ◽  
Saadia Mehmood Khan ◽  
Muhammad Muzzammil Edhi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Prognostic Significance ◽  
Breast Cancer Subtypes ◽  
Prognostic Parameters ◽  
Ki67 Index ◽  
Breast Cancers ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Cancer Management

Abstract Objectives Ki67 is the most commonly used marker to evaluate proliferative index in breast cancer, however no cutoff values have been clearly defined for high ki67 index. Cancer management should be according to loco-regional profile; therefore, we aimed to determine ki67 index in 1951 cases of intrinsic breast cancer subtypes and its association with other prognostic parameters in our set up. Results Triple negative breast cancers showed highest ki67 index (mean 50.9 ± 23.7%) followed by Her2neu (mean 42.6 ± 21.6%) and luminal B cancers (mean 34.9 ± 20.05%). Metaplastic and medullary breast cancers significantly showed higher ki67 index as compared to ductal carcinoma, NOS. No significant association of ki67 index was noted with any of the histologic parameters in different subtypes of breast cancer expect for tumor grade. Although, ki67 index is a valuable biomarker in breast cancer, however no independent prognostic significance of ki67 could be established in our study.

Young patients with breast cancer (< 35 years): Single-institution study of 194 patients from India.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11013-e11013
Author(s):  
B. K Mohanti ◽  
Vinod Raina ◽  
Ajay Gogia ◽  
S. V. S Deo ◽  
N. K Shukla
Keyword(s):  
Breast Cancer ◽  
Young Women ◽  
Ductal Carcinoma ◽  
Tumour Size ◽  
Positive Family History ◽  
Young Patients ◽  
Radical Mastectomy ◽  
Histopathological Analysis ◽  
Duration Of Symptoms ◽  
Young Breast Cancer

e11013 Background: Breast cancer in young women ( < 35 years) is uncommon and accounts for 1-2 % of all breast cancer in the West .There is paucity of data on young breast cancer from India. The aim of our study was to assess clinical and pathological parameters and outcome in young breast cancer patients. Methods: Annually we register approximately 350 new cases of breast cancer of whom young patients constitute a small fraction. This analysis was carried out in 194 patients with aged 35 years or less, who were registered in our clinic between 2000-2009, this constituted about 5.5 % of all new cases. Patients records were analysed from computer database using ICD code (C-50) Results: The median age was 31 years (range 21-35). The median duration of symptoms was 11.8 months (range 0.5-40). Breast lump was the commonest (93%) presenting symptom (left >right side). Ninety percent of patients were married and median age at first child birth was 23 years. Positive family history was elicited in 8 patients, and 3 patients presented with synchronous malignancy. The TNM (7th edition) stage distribution was stage I was 3 %, stage II- 20%, stage III- 55%, and stage IV- 22%. The median clinical tumour size was 5.9 cm. Modified Radical mastectomy was the commonest surgical procedure and this was done in 81 % of cases. The histopathological analysis showed 94% had infiltrating ductal carcinoma. Sixty percent of tumours were high grade and 56% had pathological node positive disease. ER/PR status and Her2 Neu status was available in 65% and 50% respectively. Out of these patients ER and her2neu positivity was 40% and 37% respectively. Triple negative breast cancer (TNBC) constituted 31%. A combination of anthracyclines and taxanes were used in the vast majority of patients and herceptin was used only in 5 %. With a median follow up of 30 months, three years event free (EFS) and overall survival (OS) was 50% and 60%. Higher Nodal stage, tumour size (>5 c.m ), negative ER/PR status and visceral metastasis at baseline predicted poor outcome. Conclusions: Young women constituted 5.5% cases with higher proportion of triple negativity, this is higher than the western population reflecting younger age of our population of breast cancer in general with a resultant poorer outcome.

Molecular differences between normal breast epithelia, pure DCIS, and DCIS adjacent to invasion.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 50-50
Author(s):  
Marina Guvakova
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Progression ◽  
Rho Gtpase ◽  
Ductal Carcinoma ◽  
Continuous Variable ◽  
Protein Profiling ◽  
Nucleotide Exchange ◽  
Fixed Tissue ◽  
Gene And Protein Expression

50 Background: With the use of screening mammography, the diagnosis of breast ductal carcinoma in situ (DCIS) is increasing worldwide. Currently there are no applied molecular markers to aid in predicting risk of DCIS progression to invasive breast cancer (IBC). Studies predicted that the transition from DCIS to invasive disease was associated with quantitative rather than qualitative differences in gene and protein expression. Methods: We developed monochrome imaging-based method to measure protein expression as a continuous variable in fixed tissue (Furstenau et al. BREA 2010). The insulin-like growth factor I receptor (IGF-IR), Ras oncogene –like protein 1 (Rap1), and a Rho GTPase guanine nucleotide exchange factor Vav2 implicated in the regulation of invasion in preclinical models have been chosen for protein analysis in tissue. In pilot study, we performed quantitative protein profiling on 90 samples of the breast: 17 histologically normal tissues, 16 benign lesions; 15 CIS, and 42 IBC. In addition, we analyzed 24 DCIS: 12 pure and 12 associated with IBC. Results: The expression of the IGF-IR and Rap1 was increased in pure CIS; significantly (P ≤ 0.001) increased in CIS adjacent to IBC as well as in IBC compared with non-cancerous tissue. In the majority of pure DCIS the levels of Vav2 were similar to that in normal epithelia; however, the Vav2 levels were significantly (P<0.01) higher in DCIS adjacent to invasion and in IBC. Moreover, IGF-IR, Rap1 and Vav2 significantly discriminated invasive from non-invasive tissues, with receiver operating characteristic (ROC) area under curve, AUC=0.8. Interestingly, younger women (< 50 years of age) were more likely to develop IBC with increased expression of the Vav2 protein (OR= 2.05; 95% CI 1.08-3.86). No significant correlation was found between IGF-IR, Rap1 expression levels and patient’s age. Conclusions: We conclude that our assessment of protein expression in breast tissue revealed previously unidentified quantitative differences in the IGF-IR, Rap1, and Vav2 protein expression in breast cancer progression series. These findings open door for studies on molecular-based prediction of individualized risk for developing invasion in early diagnosed DCIS.

The prognostic significance of early stage lymph node positivity in operable invasive breast carcinoma: number or stage

2012 ◽  
Vol 65 (7) ◽  
pp. 624-630 ◽  
Author(s):  
Emad A Rakha ◽  
David Morgan ◽  
Douglas Macmillan
Keyword(s):  
Breast Cancer ◽  
Prognostic Value ◽  
Independent Predictor ◽  
Early Stage ◽  
Histological Grade ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Absolute Number ◽  
Consecutive Series ◽  
Cancer Specific Survival

AimThe earlier detection of breast cancer through mammographic screening has resulted in a shift in stage distribution with patients who are node-positive tending to present with a lower number of positive lymph nodes (LN). This study aims to assess the prognostic value of absolute number of positive nodes in the pN1 TNM stage (1–3 positive LN) and whether the prognostic value of the number of nodes in this clinically important stage justifies its consideration in management decisions.MethodsThis study is based on a large and well-characterised consecutive series of operable breast cancer (3491 cases), treated according to standard protocols in a single institution, with a long-term follow-up.ResultsLN stages and the absolute number of LN are associated with both breast cancer specific survival (BCSS) and distant metastasis free survival (DMFS). In the pN1 stage, patients with three positive LN (14% of pN1) show shorter BCSS (HR=1.9, (95% CI 1.3 to 2.6)) and shorter DMFS (HR=2.2, (95% CI 1.6 to 2.9)) when compared with one and/or two positive nodes. This effect is noted in the whole series as well as in different subgroups based on tumour size (pT1c and pT2), histological grade (grade 2 and 3), vascular invasion and oestrogen receptor status (both positive and negative). Multivariable analyses showed that three positive LN, compared with one and two positive LN, are an independent predictor of shorter BCSS and DMFS.ConclusionThe number of LN in the pN1 stage yielded potentially informative risk assignments with three positive LN providing an independent predictor of poorer outcome.

scholarly journals Sharp Downregulation of Hub Genes Associated With the Pathogenesis of Breast Cancer From Ductal Carcinoma In Situ to Invasive Ductal Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yao Wang ◽  
Faqing Liang ◽  
Yuting Zhou ◽  
Juanjuan Qiu ◽  
Qing Lv ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Invasive Ductal Carcinoma ◽  
Ductal Carcinoma ◽  
Cancer Tissue ◽  
Hub Genes ◽  
Expression Levels ◽  
Cancer Pathogenesis ◽  
Ductal Hyperplasia

IntroductionBreast atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are precursor stages of invasive ductal carcinoma (IDC). This study aimed to investigate the pathogenesis of breast cancer by dynamically analyzing expression changes of hub genes from normal mammary epithelium (NME) to simple ductal hyperplasia (SH), ADH, DCIS, and finally to IDC.MethodsLaser-capture microdissection (LCM) data for NME, SH, ADH, DCIS, and IDC cells were obtained. Weighted gene co-expression network analysis (WGCNA) was performed to dynamically analyze the gene modules and hub genes associated with the pathogenesis of breast cancer. Tissue microarray, immunohistochemical, and western blot analyses were performed to determine the protein expression trends of hub genes.ResultsTwo modules showed a trend of increasing expression during the development of breast disease from NME to DCIS, whereas a third module displayed a completely different trend. Interestingly, the three modules displayed inverse trends from DCIS to IDC compared with from NME to DCIS; that is, previously upregulated modules were subsequently downregulated and vice versa. We further analyzed the module that was most closely associated with DCIS (p=7e−07). Kyoto Gene and Genomic Gene Encyclopedia enrichment analysis revealed that the genes in this module were closely related to the cell cycle (p= 4.3e–12). WGCNA revealed eight hub genes in the module, namely, CDK1, NUSAP1, CEP55, TOP2A, MELK, PBK, RRM2, and MAD2L1. Subsequent analysis of these hub genes revealed that their expression levels were lower in IDC tissues than in DCIS tissues, consistent with the expression trend of the module. The protein expression levels of five of the hub genes gradually increased from NME to DCIS and then decreased in IDC. Survival analysis predicted poor survival among breast cancer patients if these hub genes were not downregulated from DCIS to IDC.ConclusionsFive hub genes, RRM2, TOP2A, PBK, MELK, and NUSAP1, which are associated with breast cancer pathogenesis, are gradually upregulated from NME to DCIS and then downregulated in IDC. If these hub genes are not downregulated from DCIS to IDC, patient survival is compromised. However, the underlying mechanisms warrant further elucidation in future studies.

scholarly journals Comparison of ultrasound and histopatological findings breast cancer between women aged below and above 40 years.

2021 ◽  
Vol 58 (1) ◽  
pp. 5713-5722
Author(s):  
Suraini Mohamad Saini Et al.
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Ductal Carcinoma ◽  
Tumour Size ◽  
Breast Cancer Incidence ◽  
Age Group ◽  
Her2 Receptor ◽  
Cross Sectional ◽  
Common Features ◽  
Ultrasound Findings

 Breast cancer is the most common cancer among females, but breast cancer incidence in young women is low. There are limited studies of breast cancer in this age group in Malaysia, while there are conflicting data regarding these women's prognosis compared to older patients. This study describes the common features presented by breast carcinoma on histopathological and ultrasound findings. Objective: To compare the ultrasound findings and histopathological characteristics of breast cancer for women aged below 40 years and those aged 40 years and above. Methodology: This was a retrospective, cross-sectional study using secondary data, in which the data was collected respectively from patient's clinical histories, radiology findings, and histopathology reports of patients with breast cancer in Hospital Serdang from 1 January 2009 until 31 December 2018. Patients were divided into two age groups (ages below 40, ages 40 and above).  Results: 205 patients were included in this study. The most common type of breast carcinoma is invasive ductal carcinoma. Common features are grade II breast cancer cells, DCIS high grade, stage 2 (TNM), tumour size of T2 and lymph node invasion. The majority of tumours are positive with oestrogen receptor, progesterone receptor, and HER2 receptor. Conclusion: Younger age group has a similar feature with the older age group, except they have late stage and progesterone negativity. There is no significant association between age group, ultrasound, histological features, and breast carcinoma receptors. Keywords: ultrasound breast, histopathological, breast cancer

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