TP53 gene mutations in Hodgkin lymphoma are infrequent and not associated with absence of Epstein-Barr virus

Reed-Sternberg (RS) cells, the neoplastic cells of Hodgkin lymphoma (HL) ha ve clonal immunoglobulin gene rearrangements. The presence of somatic mutat ions suggests a germinal center origin, whereas the presence of crippling m utations suggests rescue of RS precursors from apoptosis by a transforming event. Epstein-Barr virus (EBV), which can be detected in 30-50% of HL case s, probably plays a role in this transforming event. The frequent presence of p53 protein expression in RS cells also suggests a role of the TP53 gene in this escape from apoptosis. Although mutations of the TP53 gene occur i nfrequently in RS cells, it has been suggested that in EBV-negative cases t his gene mutation may be fundamental for the inhibition of apoptosis. In th is study, we tested the hypothesis that there is an inverse correlation bet ween the presence of TP53 gene mutations and the presence of EBV. In 21 of 67 cases EBV encoded small RNA (EBER)1-2 mRNAs were detected. Immunostainin g for p53 protein revealed positivity in all 67 cases with variable percent ages of positive cells and staining intensity. Screening for mutations in e xons 5, 6, 7 and 8 of the TP53 gene in single RS cells obtained by laser mi crodissection from 26 HL specimens and 4 HL-derived cell lines revealed mut ations in 2 of 15 EBV-positive cases and in 1 of 11 EBV-negative cases. Our results confirm the presence of infrequent (11.5%) TP53 gene mutations in HL and suggest that mutations of the TP53 gene are not correlated to the ab sence of EBV. (C) 2001 Wiley-Liss, Inc.