HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin’s lymphoma
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Valli De Re1,*, Laura Caggiari1,*, Lara Mussolin2,**, Emanuele Stefano d’Amore3,**, Barbara Famengo3,**, Mariangela De Zorzi1, Lia Martina1, Caterina Elia4, Marta Pillon5,**, Nicola Santoro6,**, Paola Muggeo6,**, Salvatore Buffardi7,**, Maurizio Bianchi8,**, Alessandra Sala9,**, Piero Farruggia10,**, Luciana Vinti11,**, Edgardo D. Carosella12, Roberta Burnelli13,** and Maurizio Mascarin4,**
1Immunopathology and Cancer Biomarkers, Department of Translational Research, CRO Aviano National Cancer Institute, Aviano, Italy
2Clinic of Pediatric Hemato-Oncology, Department of Women’s and Children’s Health, University of Padova, Institute of Paediatric Research Fondazione Città della Speranza, Padova, Italy
3Department of Pathology, San Bortolo Hospital, Vicenza, Italy
4Pediatric Radiotherapy Unit, CRO Aviano National Cancer Institute, Aviano, Italy
5Clinic of Paediatric Hemato-Oncology, Department of Women’s and Children’s Health, University of Padova, Padova, Italy
6Department of Paediatric Hemato-Oncology, University of Bari, Bari, Italy
7Department of Paediatric Hemato-Oncology, Santobono-Pausilipon Children’s Hospital, Napoli, Italy
8Department of Paediatric Hemato-Oncology, Regina Margherita Children’s Hospital, Torino, Italy
9Department of Paediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy
10Pediatric Hematology and Oncology Unit, Oncology Department, A.R.N.A.S. Ospedali Civico, Di Cristina e Benfratelli, Palermo, Italy
11Department of Paediatric Hemato-Oncology, IRCCS Ospedale Bambino Gesù, Roma, Italy
12Department of Hemato-Immunological Research, Institut des Maladies Emergentes et des Thérapies Innovantes (iMETI), Hôpital Saint Louis, Paris, France
13Pediatric Hematology-Oncology, Azienda Ospedaliera Universitaria, Ospedale Sant’Anna, Ferrara, Italy
*These authors have contributed equally to this work
**These authors are members of the AIEOP group
Valli De Re, email: [email protected]
Keywords: pediatric hodgkin lymphoma; HLA-G; event-free survival; 3’UTR polymorphism; +3027 C/A genotype
Received: July 21, 2017 Accepted: October 28, 2017 Published: November 18, 2017
In this study, we tested whether polymorphisms in human leukocyte antigen G (HLA-G) were associated with event-free survival (EFS) in pediatric Hodgkin’s lymphoma (HL). We evaluated the association of HLA-G 3’-UTR polymorphisms with EFS in 113 pediatric HL patients treated using the AIEOP LH-2004 protocol. Patients with the +3027-C/A genotype (rs17179101, UTR-7 haplotype) showed lower EFS than those with the +3027-C/C genotype (HR= 3.23, 95%CI: 0.99-10.54, P=0.012). Female patients and systemic B symptomatic patients with the HLA-G +3027 polymorphism showed lower EFS. Multivariate analysis showed that the +3027-A polymorphism (HR 3.17, 95%CI 1.16-8.66, P=0.025) was an independent prognostic factor. Immunohistochemical analysis showed that HL cells from patients with the +3027-C/A genotype did not express HLA-G. Moreover, HLA-G +3027 polymorphism improved EFS prediction when added to the algorithm for therapeutic group classification of pediatric HL patients. Our findings suggest HLA-G +3027 polymorphism is a prognostic marker in pediatric HL patients undergoing treatment according to LH-2004 protocol.
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