HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma

Valli De Re; Laura Caggiari; Lara Mussolin; Emanuele Stefano d'Amore; Barbara Famengo; Mariangela De Zorzi; Lia Martina; Caterina Elia; Marta Pillon; Nicola Santoro; Paola Muggeo; Salvatore Buffardi; Maurizio Bianchi; Alessandra Sala; Piero Farruggia; Luciana Vinti; Edgardo D Carosella; Roberta Burnelli; Maurizio Mascarin

doi:10.18632/oncotarget.22515

HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma

Oncotarget. 2017 Nov 18;8(62):105957-105970. doi: 10.18632/oncotarget.22515. eCollection 2017 Dec 1.

Authors

Valli De Re^#¹, Laura Caggiari^#¹, 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, Maurizio Mascarin⁴

Affiliations

¹ Immunopathology and Cancer Biomarkers, Department of Translational Research, CRO Aviano National Cancer Institute, Aviano, Italy.
² Clinic 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.
³ Department of Pathology, San Bortolo Hospital, Vicenza, Italy.
⁴ Pediatric Radiotherapy Unit, CRO Aviano National Cancer Institute, Aviano, Italy.
⁵ Clinic of Paediatric Hemato-Oncology, Department of Women's and Children's Health, University of Padova, Padova, Italy.
⁶ Department of Paediatric Hemato-Oncology, University of Bari, Bari, Italy.
⁷ Department of Paediatric Hemato-Oncology, Santobono-Pausilipon Children's Hospital, Napoli, Italy.
⁸ Department of Paediatric Hemato-Oncology, Regina Margherita Children's Hospital, Torino, Italy.
⁹ Department of Paediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy.
¹⁰ Pediatric Hematology and Oncology Unit, Oncology Department, A.R.N.A.S. Ospedali Civico, Di Cristina e Benfratelli, Palermo, Italy.
¹¹ Department of Paediatric Hemato-Oncology, IRCCS Ospedale Bambino Gesù, Roma, Italy.
¹² Department of Hemato-Immunological Research, Institut des Maladies Emergentes et des Thérapies Innovantes (iMETI), Hôpital Saint Louis, Paris, France.
¹³ Pediatric Hematology-Oncology, Azienda Ospedaliera Universitaria, Ospedale Sant'Anna, Ferrara, Italy.

^# Contributed equally.

Abstract

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.

Keywords: +3027 C/A genotype; 3’UTR polymorphism; HLA-G; event-free survival; pediatric hodgkin lymphoma.