Carlos López1,2, Ramón Bosch3, Anna Korzynska4, Marcial García-Rojo5, Gloria Bueno6, Joan Francesc García-Fontgivell7, Salomé Martínez González7, Andrea Gras Navarro3,8, Esther Sauras Colón9, Júlia Casanova Ribes3, Lukasz Roszkowiak4, Daniel Mata3, Meritxell Arenas10, Junior Gómez10, Albert Roso11, Marta Berenguer12, Silvia Reverté-Villarroya8,12, Montserrat Llobera13, Jordi Baucells14, Marylène Lejeune3,8. 1. Department of Pathology, Oncological Pathology and Bioinformatics Research Group, Hospital de Tortosa Verge de la Cinta, ICS, IISPV, C/Esplanetes no 14, 43500, Tortosa, Spain. clopezp.ebre.ics@gencat.cat. 2. Universitat Rovira i Virgili (URV) - Campus Terres de l'Ebre, Avinguda Remolins no 13-15, 43500, Tortosa, Spain. clopezp.ebre.ics@gencat.cat. 3. Department of Pathology, Oncological Pathology and Bioinformatics Research Group, Hospital de Tortosa Verge de la Cinta, ICS, IISPV, C/Esplanetes no 14, 43500, Tortosa, Spain. 4. Laboratory of Processing and Analysis of Microscopic Images, Polish Academy of Sciences (IBIB PAN), Nalęcz Institute of Biocybernetics and Biomedical Engineering, Ks. Trojdena 4 St., 02-109, Warsaw, Poland. 5. Department of Pathology, Hospital Universitario Puerta del Mar, Avda. Ana de Viya, 21, 11009, Cádiz, Spain. 6. VISILAB, Universidad de Castilla-La Mancha, Av. Camilo José Cela, s/n, 13071, Ciudad Real, Spain. 7. Department of Pathology, Hospital Universitari Joan XXIII, C/Dr. Mallafrè Guasch, 4, 43005, Tarragona, Spain. 8. Universitat Rovira i Virgili (URV) - Campus Terres de l'Ebre, Avinguda Remolins no 13-15, 43500, Tortosa, Spain. 9. Department of Pathology, Oncological Pathology and Bioinformatics Research Group, Hospital de Tortosa Verge de la Cinta, ICS, IISPV, C/Esplanetes no 14, 43500, Tortosa, Spain. esthersauras.96@gmail.com. 10. Institut d'Investigació Sanitària Pere Virgili, Radiation Oncology Department, Universitat Rovira i Virgili, Hospital Universitari Sant Joan de Reus, Reus, Spain. 11. Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Gran Via Corts Catalanes, 587, 08007, Barcelona, Spain. 12. Knowledge Management Department, Hospital de Tortosa Verge de la Cinta, ICS, IISPV, C/Esplanetes no 14, 43500, Tortosa, Spain. 13. Department of Oncology, Hospital de Tortosa Verge de la Cinta, ICS, IISPV, C/Esplanetes no 14, 43500, Tortosa, Spain. 14. Informatics Department, Hospital de Tortosa Verge de la Cinta, ICS, IISPV, C/Esplanetes no 14, 43500, Tortosa, Spain.
Abstract
BACKGROUND: The foremost cause of death of breast cancer (BC) patients is metastasis, and the first site to which BC predominantly metastasizes is the axillary lymph node (ALN). Thus, ALN status is a key prognostic indicator at diagnosis. The immune system has an essential role in cancer progression and dissemination, so its evaluation in ALNs could have significant applications. In the present study we aimed to investigate the association of clinical-pathological and immune variables in the primary tumour and non-metastatic ALNs (ALNs-) of a cohort of luminal A and triple-negative BC (TNBC) patients with cancer-specific survival (CSS) and time to progression (TTP). METHODS: We analysed the differences in the variables between patients with different outcomes, created univariate and multivariate Cox regression models, validated them by bootstrapping and multiple imputation of missing data techniques, and used Kaplan-Meier survival curves for a 10-years follow-up. RESULTS: We found some clinical-pathological variables at diagnosis (tumour diameter, TNBC molecular profile and presence of ALN metastasis), and the levels of several immune markers in the two studied sites, to be associated with worse CSS and TTP. Nevertheless, only CD68 and CD83 in ALNs- were confirmed as independent prognostic factors for TTP. CONCLUSIONS: The study identified the importance of macrophage and dendritic cell markers as prognostic factors of relapse for BC. We highlight the importance of studying the immune response in ALNs-, which could be relevant to the prediction of BC patients' outcome.
BACKGROUND: The foremost cause of death of breast cancer (BC) patients is metastasis, and the first site to which BC predominantly metastasizes is the axillary lymph node (ALN). Thus, ALN status is a key prognostic indicator at diagnosis. The immune system has an essential role in cancer progression and dissemination, so its evaluation in ALNs could have significant applications. In the present study we aimed to investigate the association of clinical-pathological and immune variables in the primary tumour and non-metastatic ALNs (ALNs-) of a cohort of luminal A and triple-negative BC (TNBC) patients with cancer-specific survival (CSS) and time to progression (TTP). METHODS: We analysed the differences in the variables between patients with different outcomes, created univariate and multivariate Cox regression models, validated them by bootstrapping and multiple imputation of missing data techniques, and used Kaplan-Meier survival curves for a 10-years follow-up. RESULTS: We found some clinical-pathological variables at diagnosis (tumour diameter, TNBC molecular profile and presence of ALN metastasis), and the levels of several immune markers in the two studied sites, to be associated with worse CSS and TTP. Nevertheless, only CD68 and CD83 in ALNs- were confirmed as independent prognostic factors for TTP. CONCLUSIONS: The study identified the importance of macrophage and dendritic cell markers as prognostic factors of relapse for BC. We highlight the importance of studying the immune response in ALNs-, which could be relevant to the prediction of BC patients' outcome.
Authors: R Salgado; C Denkert; S Demaria; N Sirtaine; F Klauschen; G Pruneri; S Wienert; G Van den Eynden; F L Baehner; F Penault-Llorca; E A Perez; E A Thompson; W F Symmans; A L Richardson; J Brock; C Criscitiello; H Bailey; M Ignatiadis; G Floris; J Sparano; Z Kos; T Nielsen; D L Rimm; K H Allison; J S Reis-Filho; S Loibl; C Sotiriou; G Viale; S Badve; S Adams; K Willard-Gallo; S Loi Journal: Ann Oncol Date: 2014-09-11 Impact factor: 32.976
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Authors: Luis de la Cruz-Merino; Antonio Barco-Sánchez; Fernando Henao Carrasco; Esteban Nogales Fernández; Ana Vallejo Benítez; Javier Brugal Molina; Antonio Martínez Peinado; Ana Grueso López; Manuel Ruiz Borrego; Manuel Codes Manuel de Villena; Víctor Sánchez-Margalet; Adoración Nieto-García; Emilio Alba Conejo; Noelia Casares Lagar; José Ibáñez Martínez Journal: Clin Dev Immunol Date: 2013-06-03
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