IGH AND TCR-GAMMA GENE REARRANGEMENTS IDENTIFIED IN HODGKINS-DISEASE BY PCR DEMONSTRATE LACK OF CORRELATION BETWEEN GENOTYPE, PHENOTYPE, EPSTEIN-BARR-VIRUS STATUS

Analysis of IgH and TcR-gamma genes using consensus primers identifyin g junctional regions of rearranged genes by polymerase chain reaction (PCR) was performed on tissues involved by Hodgkin's disease (HD) in 9 0 cases and was correlated with the immunophenotype of Hodgkin and Ree d-Sternberg (HRS) cells and the presence of Epstein-Barr virus (EBV) w ithin these cells. Clonal IgH gene rearrangements were found in 1/5 ca ses of lymphocyte predominance (LP) subtype and none was positive for EBV. In 85 cases of classic HD, no IgH or TcR-gamma gene rearrangement s were found in 51 (60 per cent) cases. A similar percentage, but not the same cases, were of null (non-B, non-T) phenotype. Of 30 cases whe re a B phenotype was assigned to HRS cells, nine had IgH gene rearrang ements, three had TcR-gamma gene rearrangements, and two had both gene s rearranged. None of the five gases assigned to T phenotype of HRS ce lls showed rearrangement of TcR-gamma genes, but two cases showed rear ranged IgH genes. Among 41 cases of null phenotype, ten had IgH gene r earrangements, five had TcR-gamma gene rearrangements, and three cases had both genes rearranged. Whereas EBV was detectable in HRS cells in 17/43 classic HD cases of assigned B phenotype, EBV was also detectab le in 2/5 cases of assigned T phenotype and in 21 cases with the null phenotype. Furthermore, there was no correlation of EBV with the prese nce or lack of IgH or TCR-gamma gene rearrangements. Of the remainder, half (30 per cent) expressed antigens associated with lymphocytes wit hout an appropriate genotype. The results confirm lymphocyte-lineage c ommitted cells at the origin of HRS cells in 40 per cent of cases. Any hypothesis of a non-lymphocytic origin of HRS cells will require the inducibility of CD30 on candidate precursors and the methodology for p robing genetic events in such cells to be addressed. (C) 1997 by John Wiley & Sons, Ltd .