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 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 Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer

2019 ◽  
Vol 121 (9) ◽  
pp. 776-785 ◽  
Author(s):  
Chitra Joseph ◽  
Sara Al-Izzi ◽  
Mansour Alsaleem ◽  
Sasagu Kurozumi ◽  
Michael S Toss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Patient Outcome ◽  
Distant Metastasis ◽  
Prognostic Significance ◽  
Retinoid X Receptor ◽  
Cancer Tissue ◽  
Lower Grade ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Er Positive

Abstract Background Retinoid X Receptor Gamma (RXRG) is a member of the nuclear receptor superfamily and plays a role in tumour suppression. This study aims to explore the prognostic significance of RXRG in breast cancer. Methods Primary breast cancer tissue microarrays (n = 923) were immuno-stained for RXRG protein and correlated with clinicopathological features, and patient outcome. Results Nuclear RXRG expression was significantly associated with smaller tumour size (p = 0.036), lower grade (p < 0.001), lobular histology (p = 0.016), lower Nottingham Prognostic Index (p = 0.04) and longer breast cancer-specific survival (p < 0.001), and longer time to distant metastasis (p = 0.002). RXRG expression showed positive association with oestrogen receptor (ER)-related biomarkers: GATA3, FOXA1, STAT3 and MED7 (all p < 0.001) and a negative correlation with the Ki67 proliferation marker. Multivariate analysis demonstrated RXRG protein as an independent predictor of longer breast cancer-specific survival and distant metastasis-free survival. In the external validation cohorts, RXRG expression was associated with improved patients’ outcome (p = 0.025). In ER-positive tumours, high expression of RXRG was associated with better patient outcome regardless of adjuvant systemic therapy. ER signalling pathway was the top predicted master regulator of RXRG protein expression (p = 0.005). Conclusion This study provides evidence for the prognostic value of RXRG in breast cancer particularly the ER-positive tumours.

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 Immunohistochemical Expressions of Senescence-Associated Secretory Phenotype and Its Association With Immune Microenvironments and Clinicopathological Factors in Invasive Breast Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Min Hui Park ◽  
Jung Eun Choi ◽  
Jae-Ryong Kim ◽  
Young Kyung Bae
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Molecular Subtype ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Ki 67 ◽  
Entire Cohort ◽  
Secretory Phenotype

This study was undertaken to investigate immunohistochemical expression of the senescence-associated secretory phenotype (SASP) in invasive breast cancer (IBC) tissues and to determine relationships between SASP positivity and tumor microenvironments and the clinicopathological characteristics of IBC. Immunohistochemistry for senescence markers, that is, high mobility group box-1 (HMGB1), p16, p15, and decoy receptor 2 (DCR2), was performed in tissue microarrays of 1140 IBC samples. Cases positive for at least one of these four markers were considered SASP-positive. Relations between SASP and tumor characteristics, including immune microenvironments (stromal tumor-infiltrating lymphocytes [sTILs] density and numbers of intraepithelial CD103-positive [iCD103 + ] lymphocytes) and clinical outcomes were retrospectively evaluated. HMGB1, p16, p15, or DCR2 was positive in 6.7%, 26.6%, 21.1%, and 26.5%, respectively, of the 1,140 cases. Six hundred and five (53.1%) cases were SASP positive, and SASP positivity was significantly associated with histologic grade 3, high-sTIL and iCD103 + lymphocyte counts, absence of ER or PR, and a high Ki-67 index. Although SASP did not predict breast cancer-specific survival (BCSS) or disease-free survival (DFS) in the entire cohort, SASP positivity in luminal A IBC was associated with poor BCSS and DFS. However, patients with SASP-positive TNBC showed better survival than those with SASP-negative TNBC. In multivariate analysis, SASP positivity was an independent prognostic factor in both luminal A IBC and TNBC, although the effect on prognosis was the opposite. In conclusion, SASP would be involved in the modulation of immune microenvironments and tumor progression in IBC, and its prognostic significance depends on molecular subtype.

scholarly journals Clinicopathologic and Prognostic Significance of Transducin-Like Enhancer of Split 1 Protein Expression in Invasive Breast Cancer

2017 ◽  
Vol 20 (1) ◽  
pp. 45 ◽  
Author(s):  
Ji-Hye Lee ◽  
Sang Byung Bae ◽  
Mee-Hye Oh ◽  
Hyun Deuk Cho ◽  
Si-Hyong Jang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Invasive Breast Cancer ◽  
Prognostic Significance ◽  
Enhancer Of Split

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.

Use of multiplex mutation genotyping to identify novel and protective mutations in breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11004-11004
Author(s):  
K. Kalinsky ◽  
L. M. Jacks ◽  
C. Hedvat ◽  
U. Bhanot ◽  
S. Patil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pik3ca Mutation ◽  
Prognostic Significance ◽  
Predictive Biomarkers ◽  
Breast Tumors ◽  
Tumor Biomarker ◽  
Lower Grade ◽  
Cancer Specific Survival ◽  
Mutation Status ◽  
Pik3ca Mutations

11004 Background: We recently analyzed 590 primary invasive breast tumors for PIK3CA mutations by multiplex massARRAY genotyping. We identified a 32.5% PIK3CA mutation rate (manuscript submitted). Associations between PIK3CA mutation status and favorable pathology, such as lower grade tumors, lymph node negativity and hormone receptor (HR) positivity, were observed. Multiplex analysis allows the rapid assessment of mutations not commonly described in breast cancer. To identify activated pathways that may serve as predictive biomarkers, tissue microarrays (TMA) underwent immunohistochemical (IHC) analysis. Methods: 590 archival formalin-fixed paraffin embedded (FFPE) tumors > 1 cm were used to ensure adequate tissue procurement for mutation detection and TMA construction. MassARRAY (Sequenom) genotyping was performed on native DNA to identify PIK3CA, RAS, RET, and other known mutations. IHC staining of the TMAs included assessment of steroid nuclear receptors, HER2 expression, Akt pathway activation (including pAKT, p70S6K, eIF4E), and PTEN. Stained TMAs underwent digital quantitative image analysis and scoring (Aperio, Vista, CA). The Kaplan-Meier method and Cox models were used in univariate and multivariate analysis for associations of mutation status and clinicopathologic features on overall survival (OS) and breast cancer-specific survival (BCSS). Results: Compared to wild-type, PIK3CA mutated tumors (median f/u: 12.8 years) demonstrate a significant improvement in OS (p=0.03) and BCSS (p=0.004). For patients with any PIK3CA mutation, the improvement in BCSS is maintained in HR positive and ER negative subgroups. In addition to PIK3CA mutations, RAS and RET mutations are identified in a small proportion of breast tumors. Additional analysis to evaluate the association of mutation status and biomarker data derived from the TMA analysis will be performed for meeting presentation. Conclusions: We have recently defined the positive prognostic significance of PIK3CA mutations in breast cancer. RAS mutations are confirmed to occur rarely in breast cancer. The finding of RET mutations in breast cancer is novel. Future tumor biomarker identification directed towards predictive measurement will assist in tailoring therapy to appropriate patient populations. No significant financial relationships to disclose.

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 Molecular and clinical characterization of CCT2 expression at transcriptional level via 2994 samples of breast cancer

2020 ◽  
Author(s):  
Qiang Liu ◽  
Yihang Qi ◽  
Xiangyu Wang ◽  
Xiangyi Kong ◽  
Yi Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Molecular Taxonomy ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Transcriptional Level ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Worse Prognosis

Abstract BackgroundMolecular chaperones play important roles in regulating various cellular processes and malignant transformation. Expression of some subunits of molecular chaperonen CCT/TRiC complex have been reported to be correlated with cancer development and patient survival. However, little is known about the expression and prognostic significance of Chaperonin Containing TCP1 Subunit 2 (CCT2), a gene encoding a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC).MethodThrough the Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, we systematically reviewed a total of 2994 cases with transcriptome data and analyzed the functional annotation of CCT2 by Gene ontology (GO) and KEGG analysis. Univariate and multivariate survival analysis were performed to investigate the prognostic value of CCT2 in breast cancer.ResultsWe found CCT2 was significantly upregulated in various tumors. In breast cancer, CCT2 expression was significantly upregulated in HER2-positive (HER2+) group, and more malignant group. In addition, we investigated correlations between CCT2 and other CCT members. Interestingly, almost all CCTs expression were positively correlated with each other, but not CCT6B. Survival analysis suggested that CCT2 overexpression was independently associated with worse prognosis of patients with breast cancer, especially in luminal A subtype.ConclusionIn summary, our results revealed that CCT2 might be involved in regulating cell cycle pathway, and independently predicted worse prognosis in breast cancer patients. These findings may expand understanding of potential anti-CCT2 treatments. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of CCT2 together with its prognostic values in breast cancer.

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