Infección por el virus de epstein barr en pacientes pediátricos y adultos afectos de linfoma de hodgkin: estudio epidemiológico y alteraciones asociadas del ciclo celular y la apoptosis

Abstract

Context Classical Hodgkin lymphoma (cHL) is a malignant tumour with clinical, epidemiological and biological unique properties. Many studies characterized the behaviour of the disease, showing differences between children and adults, and also depending on socioeconomic factors. Substantial evidence that Hodgkin and Reed Sternberg (HRS) cells have defects in cell cycle and apoptosis regulation. Furthermore, the Epstein Barr virus (EBV) has shown to play a pathogenetic role in cHL. Published data studying the relationship between alterations in cell cycle and apoptosis depending on age and EBV status are limited. Aims This study aimed to investigate the epidemiology of cHL in our population and the expression of cell cycle and apoptosis proteins, correlating with the age and the status of VEB. Patients and methods We studied 94 cHL cases divided into three age groups. Epidemiological aspects were recorded. The presence of the EBV was analysed in the biopsies samples by immunohistoquimical, in situ hybridation and polymerase chain reaction (PCR) techniques. The concordance of these techniques was evaluated. We analysed the expression of cyclin A, cyclin B, cyclin D1, cyclin E, p16, p21, p27, p53, bcl-2, bcl-xl and bax by tissue microarray (TMA). Results EBV was present in HRS cells in 47% of the cases, especially in patients under 10 and over 60 years old. Determination of EBV by LMP1 (latent membrane protein 1) and EBER (EBV-encoded RNA) showed high concordance. Multiple alterations were observed in cell cycle and apoptosis proteins distinguished by overexpression of cyclin E, cyclin A and p16 and underexpression of p27, p53 and bcl-2. The results revealed specific immunohistochemical profile in each group of age. The presence of EBV was also associated with a characteristic expression profile and had a modulator effect on the relations of inductors and inhibitors of the cell cycle. EBV presence and age between 0 and 20 years old were associated with favourable survival. Overexpression of cyclin D1 and bcl-xl was associated with poorer survival. Conclusion This study demonstrates that HRS cells show significant alterations in cell cycle and apoptosis that differs depending on age and EBV status. This data would suggest that these are biologically distinct disease entities.

Date of Award	23 Jul 2014
Original language	Spanish
Supervisor	Carlos Rodrigo Gonzalo de Liria (Director)