Evangelia Razis1, Konstantine T Kalogeras2, Ioannis Kotsantis3, Georgia-Angeliki Koliou4, Kyriaki Manousou4, Ralph Wirtz5, Elke Veltrup5, Helen Patsea6, Nikiforita Poulakaki7, Dimitrios Dionysopoulos8, Stavroula Pervana9, Helen Gogas10, Angelos Koutras11, George Pentheroudakis12, Christos Christodoulou13, Helena Linardou14, Kitty Pavlakis15, Triantafyllia Koletsa16, Dimitrios Pectasides17, Flora Zagouri18, George Fountzilas19. 1. Third Department of Medical Oncology, Hygeia Hospital, Athens, Greece. Electronic address: e.razis@hygeia.gr. 2. Translational Research Section, Hellenic Cooperative Oncology Group, Athens, Greece; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece. 3. Section of Medical Oncology, Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 4. Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece. 5. STRATIFYER Molecular Pathology GmbH, Cologne, Germany. 6. Department of Pathology, IASSO General Hospital, Athens, Greece. 7. Breast Surgery Clinic, Euroclinic, Athens, Greece. 8. Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece. 9. Department of Pathology, Papageorgiou Hospital, Thessaloniki, Greece. 10. First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 11. Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece. 12. Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece. 13. Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece. 14. Oncology Unit, Metropolitan Hospital, Piraeus, Greece. 15. Pathology Department, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 16. Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece. 17. Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece. 18. Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 19. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece; Aristotle University of Thessaloniki, Thessaloniki, Greece.
Abstract
BACKGROUND: Chemokines, cytokines in the immune microenvironment of tumors, may be associated with patient outcome. We assessed the impact of CXCL13 and CXCL9 on disease-free (DFS) and overall survival (OS), in an attempt to retrospectively evaluate both T and B cell function in the microenvironment of primary tumors from patients with breast cancer. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue blocks from patients with intermediate/high-risk, early breast cancer, treated with sequential adjuvant epirubicin, paclitaxel, and cyclophosphamide methotrexate fluorouracil within a randomized trial, were tested for CXCL13 and CXCL9 messenger RNA expression; 557 patients with adequate tissue were eligible for the analysis. RESULTS: CXCL13 was correlated with CXCL9 (rho = 0.52; P < .001). High-expressing CXL13 and CXCL9 tumors had higher Ki67 and tumor infiltrating lymphocyte density (P-values < .001). High CXCL9 expression was an unfavorable prognosticator for OS among all patients (hazard ratio [HR], 1.73; P = .021), whereas it showed favorable significance for both DFS and OS in patients with triple negative disease (HR, 0.29; P = .027 and HR, 0.32; P = .045). High CXCL13 conferred longer DFS and OS among patients with luminal-human epidermal growth factor receptor 2 disease (HR, 0.31; P = .013 and HR, 0.25; P = .005). Patients with low CXCL13 and high CXCL9 expression had shorter DFS and OS compared with those with high expression of both chemokines (HR, 1.63; P = .006 and HR, 1.61; P = .016). CONCLUSIONS: Both biomarkers were associated with poor prognosis characteristics and with tumor infiltrating lymphocyte density. High CXCL9 conferred an improved prognosis in the triple negative subtype, whereas high CXCL13 was associated with improved outcome in the luminal-human epidermal growth factor receptor 2 subtype. Chemokines can be associated with breast cancer subtype and outcome. These data should be evaluated prospectively.
BACKGROUND: Chemokines, cytokines in the immune microenvironment of tumors, may be associated with patient outcome. We assessed the impact of CXCL13 and CXCL9 on disease-free (DFS) and overall survival (OS), in an attempt to retrospectively evaluate both T and B cell function in the microenvironment of primary tumors from patients with breast cancer. MATERIALS AND METHODS:Formalin-fixed paraffin-embedded tissue blocks from patients with intermediate/high-risk, early breast cancer, treated with sequential adjuvant epirubicin, paclitaxel, and cyclophosphamide methotrexate fluorouracil within a randomized trial, were tested for CXCL13 and CXCL9 messenger RNA expression; 557 patients with adequate tissue were eligible for the analysis. RESULTS:CXCL13 was correlated with CXCL9 (rho = 0.52; P < .001). High-expressing CXL13 and CXCL9tumors had higher Ki67 and tumor infiltrating lymphocyte density (P-values < .001). High CXCL9 expression was an unfavorable prognosticator for OS among all patients (hazard ratio [HR], 1.73; P = .021), whereas it showed favorable significance for both DFS and OS in patients with triple negative disease (HR, 0.29; P = .027 and HR, 0.32; P = .045). High CXCL13 conferred longer DFS and OS among patients with luminal-humanepidermal growth factor receptor 2 disease (HR, 0.31; P = .013 and HR, 0.25; P = .005). Patients with low CXCL13 and high CXCL9 expression had shorter DFS and OS compared with those with high expression of both chemokines (HR, 1.63; P = .006 and HR, 1.61; P = .016). CONCLUSIONS: Both biomarkers were associated with poor prognosis characteristics and with tumor infiltrating lymphocyte density. High CXCL9 conferred an improved prognosis in the triple negative subtype, whereas high CXCL13 was associated with improved outcome in the luminal-humanepidermal growth factor receptor 2 subtype. Chemokines can be associated with breast cancer subtype and outcome. These data should be evaluated prospectively.
Authors: Mahmood Yaseen Hachim; Ibrahim Yaseen Hachim; Iman M Talaat; Nada M Yakout; Rifat Hamoudi Journal: Front Immunol Date: 2020-11-16 Impact factor: 7.561
Authors: Lauren C Peres; Mary K Townsend; Brenda M Birmann; Jose R Conejo-Garcia; Yongjoo Kim; Laura D Kubzansky; Larry I Magpantay; Otoniel Martinez-Maza; Shelley S Tworoger Journal: Cancer Epidemiol Biomarkers Prev Date: 2021-02-09 Impact factor: 4.254
Authors: Eda G Ramirez-Valles; Alicia Rodríguez-Pulido; Marcelo Barraza-Salas; Isaac Martínez-Velis; Iván Meneses-Morales; Víctor M Ayala-García; Carlos A Alba-Fierro Journal: Technol Cancer Res Treat Date: 2020 Jan-Dec