Variable Expression of Notch1 and Pax5 in Classical Hodgkin Lymphoma and Infection with Epstein-Barr in Pediatric Patients.

Icela Palma-Lara,Juan Carlos Núñez-Enríquez,Alejandra Contreras-Ramos,Octavio Martínez-Villegas,Sergio Zavala-Vega,Guillermo Mora-Ramiro,Ana Elena Sánchez-Aldana,José Refugio Torres-Nava,Elva Jiménez-Hernández,Sara A Ochoa,José Arellano-Galindo,Juan Xicohtencatl-Cortes,Mariana García-Jiménez,Juan Manuel Mejía-Aranguré,Ariadnna Cruz-Córdova

doi:10.3390/microorganisms8060958

Abstract

NOTCH1 and PAX5 participate in the proliferation and differentiation of B and T lymphocytes. Their expression can be modified by activation of NOTCH1, induced by the Epstein–Barr (EBV) viral proteins identified as LMP1 and LMP2. To identify whether PAX5, NOTCH1, and EBV latency genes participate in the oncogenic process of pediatric patients with classical Hodgkin lymphoma (cHL), the present study aimed to identify the variable expression of NOTCH1 among disease subtypes and to assess its effect on PAX5 expression. A total of 41 paraffin-embedded tissues from Mexican pediatric patients with cHL were analyzed. The expression of CD30, CD20, NOTCH1, PAX5, and LMP1 was evaluated by immunohistochemistry and immunofluorescence. EBV detection was performed by in situ hybridization. Out of all cases, 78% (32/41) of the cHL cases were EBV positive. NOTCH1 expression was detected in 78.1% (25/32) of EBV-positive cases, nodular sclerosis being the most frequent subtype (11/25, 44%). In cases where the expression of both genes was identified, double immunofluorescence assays were conducted, finding no colocalization. We found that Reed–Sternberg cells had aberrant expression compared to their cells of origin (B lymphocytes) due to the molecular mechanisms involved in the loss of expression of PAX5 and that the identification of NOTCH1 could be considered as a candidate diagnostic/prognostic marker and a therapeutic target in pediatric cHL.

Highlights

In Mexico, hematologic neoplasms represent a significant cause of death in the pediatric population [1]
To identify whether PAX5, NOTCH1, and Epstein–Barr virus (EBV) infection participate in the oncogenic process of classical Hodgkin lymphoma, the present study aimed to identify the variable expression of NOTCH1 among disease subtypes and to assess its effect on PAX5 expression
NOTCH1 is repressed by PAX5; aberrant expression of NOTCH1 interferes with the B lymphoid phenotype of neoplastic B cells in the classical Hodgkin lymphoma [11,17]

Summary

Introduction

In Mexico, hematologic neoplasms represent a significant cause of death in the pediatric population [1]. Hodgkin lymphoma (HL) represents one of the most frequent types of childhood cancer It is classified into two groups: (a) the classical Hodgkin lymphoma (cHL), which represents 95% of cases, and (b) the nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) variety, which represents around 5% of cases [2]. The classical form can be classified into four subtypes based on the Reed–Sternberg cell (RSC) morphology and the composition of the reactive cell infiltrate observed in the lymph node biopsy specimen. These subtypes are (1) Nodular sclerosis Hodgkin lymphoma (NSHL), (2) mixed cellularity (MCHL), (3) lymphocyte-rich, and (4) lymphocyte-depleted forms (LDHL) [2]. In some countries, the virus has been detected in 50% of Reed–Sternberg cells (RSCs), whereas in others, the frequency can reach up to 77% [5]

Methods

Results

Conclusion