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

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.

Epstein-Barr virus: Causes, consequenses, diagnosis and treatment of Epstein-Barr virus in human

“…Some studies that have been carried out so far have shown that the percentage of viruses in Reed-Sternberg cells that are pathognomonic for Hodgkin's lymphoma, and that possessed a given virus, ranges up to over 70%. More precisely, over 70% of Reed-Sternberg cells and Stennerberg's cells had Epstein-Barr virus in them (19).…”

Special Issue: Epstein–Barr–Virus–Associated Cancers

“…This Special Issue assembles eleven papers, comprising seven research articles, two reviews, and two brief reports, which collectively provide novel information on the mechanisms of oncogenesis [ 2 , 3 , 4 , 5 , 6 ] and viral replication [ 7 , 8 , 9 , 10 ], as well as applications for diagnosis [ 11 , 12 ].…”

“…Using a variety of methods and approaches, several studies have provided a novel notion in understanding how EBV contributes to the development of various tumors, including GC [ 2 , 3 ], HL [ 4 ], NPC [ 5 ], and oral squamous cell carcinoma [ 6 ], on a molecular basis. A distinct feature of EBV-associated GC is the significant infiltration of immune cells in the epithelium, which appears to establish a unique tumor microenvironment.…”

“…Bioinformatic approaches revealed that an EBV-encoded microRNA, miR-BART17-5p, directly downregulates Kruppel-like factor 2 in EBV-associated GC cells, which subsequently confers an oncogenic phenotype [ 3 ]. Other studies identified host factors such as Notch1 and Pax5 or Semaphorin 3A, which exhibited correlated expression with viral infection in EBV-associated HL [ 4 ] or NPC [ 5 ], respectively, indicating that they could be considered as a candidate diagnostic/prognostic marker and a therapeutic target in these tumors. EBV establishes latent infection in squamous cell carcinoma cell lines, suggesting that it can be used as an in vitro model to investigate the role of EBV in the development of uncharacterized oral squamous cell carcinoma [ 6 ].…”