Chitra Joseph1, Maariya Arshad1, Sasagu Kurozomi1,2, Maryam Althobiti1, Islam M Miligy1,3, Sara Al-Izzi1, Michael S Toss1,3, Fang Qin Goh1, Simon J Johnston1, Stewart G Martin1, Ian O Ellis1,4, Nigel P Mongan5,6, Andrew R Green1, Emad A Rakha7,8,9. 1. Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK. 2. Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan. 3. Histopathology Department, Faculty of Medicine, Menoufia University, Shebin El-kom, Al Minufiyah, Egypt. 4. Department of Histopathology, School of Medicine, Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, NG5 1PB, UK. 5. Cancer Biology and Translational Research, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK. 6. Department of Pharmacology, Weill Cornell Medicine, 10065, New York, NY, USA. 7. Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK. Emad.Rakha@nottingham.ac.uk. 8. Histopathology Department, Faculty of Medicine, Menoufia University, Shebin El-kom, Al Minufiyah, Egypt. Emad.Rakha@nottingham.ac.uk. 9. Department of Histopathology, School of Medicine, Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, NG5 1PB, UK. Emad.Rakha@nottingham.ac.uk.
Abstract
PURPOSE: CD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic value of CD133 expression in early invasive BC. METHODS: CD133 mRNA was assessed in the METABRIC cohort and at the proteomic level using immunohistochemistry utilising a large well-characterised BC cohort. Association with clinicopathological characteristics, expression of other stem cell markers and patient outcome were evaluated. RESULTS: High expression of CD133 either in mRNA or protein levels was associated with characteristics of poor prognosis including high tumour grade, larger tumour size, high Nottingham Prognostic Index, HER2 positivity and hormonal receptor negativity (all; p < 0.001). High CD133 expression was positively associated with proliferation biomarkers including p16, Cyclin E and Ki67 (p < 0.01). Tumours expressing CD133 showed higher expression of other stem cell markers including CD24, CD44, SOX10, ALDHA3 and ITGA6. High expression of CD133 protein was associated with shorter BC-specific survival (p = 0.026). Multivariate analysis revealed that CD133 protein expression was an independent risk factor for shorter BC-specific survival (p = 0.038). CONCLUSION: This study provides evidence for the prognostic value of CD133 in invasive BC. A strong positive association of BC stem cell markers is observed at the protein level. Further studies to assess the value of stem cell markers individually or in combination in BC is warranted.
PURPOSE:CD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic value of CD133 expression in early invasive BC. METHODS:CD133 mRNA was assessed in the METABRIC cohort and at the proteomic level using immunohistochemistry utilising a large well-characterised BC cohort. Association with clinicopathological characteristics, expression of other stem cell markers and patient outcome were evaluated. RESULTS: High expression of CD133 either in mRNA or protein levels was associated with characteristics of poor prognosis including high tumour grade, larger tumour size, high Nottingham Prognostic Index, HER2 positivity and hormonal receptor negativity (all; p < 0.001). High CD133 expression was positively associated with proliferation biomarkers including p16, Cyclin E and Ki67 (p < 0.01). Tumours expressing CD133 showed higher expression of other stem cell markers including CD24, CD44, SOX10, ALDHA3 and ITGA6. High expression of CD133 protein was associated with shorter BC-specific survival (p = 0.026). Multivariate analysis revealed that CD133 protein expression was an independent risk factor for shorter BC-specific survival (p = 0.038). CONCLUSION: This study provides evidence for the prognostic value of CD133 in invasive BC. A strong positive association of BC stem cell markers is observed at the protein level. Further studies to assess the value of stem cell markers individually or in combination in BC is warranted.
Entities:
Keywords:
CD133; Cancer Stem Cell; Invasive breast cancer; Prognosis
Authors: Maryam Althobiti; Abir A Muftah; Mohammed A Aleskandarany; Chitra Joseph; Michael S Toss; Andrew Green; Emad Rakha Journal: Breast Cancer Res Treat Date: 2020-06-10 Impact factor: 4.872
Authors: Chitra Joseph; Mansour Alsaleem; Nnamdi Orah; Pavan L Narasimha; Islam M Miligy; Sasagu Kurozumi; Ian O Ellis; Nigel P Mongan; Andrew R Green; Emad A Rakha Journal: Breast Cancer Res Treat Date: 2020-05-22 Impact factor: 4.872
Authors: Sook-Kyoung Heo; Eui-Kyu Noh; Lan Jeong Ju; Jun Young Sung; Yoo Kyung Jeong; Jaekyung Cheon; Su Jin Koh; Young Joo Min; Yunsuk Choi; Jae-Cheol Jo Journal: BMC Cancer Date: 2020-04-06 Impact factor: 4.430
Authors: Cathrine Elisabeth Olsen; Lawrence H Cheung; Anette Weyergang; Kristian Berg; Daniel A Vallera; Michael G Rosenblum; Pål Kristian Selbo Journal: J Clin Med Date: 2019-12-26 Impact factor: 4.241