Fas ligand expression in Hodgkin lymphoma

Because previous investigations suggested involvement of the Fas ligand (Fa sL) in the selection process in the follicular dendritic cell (FDC)-associa ted cell cluster of the germinal center, we investigated the expression of FasL in Hodgkin lymphoma (HL) on protein and RNA level, while considering t he Epstein-Barr: virus status of the Hodgkin and Reed-Sternberg (HRS) cells . Tumor tissue from 47 patients with classic HL (32 nodular sclerosis [NS], 11 mixed cellularity [MC], and 4 lymphocyte-rich [LR]) was analyzed by imm unohistochemistry for FasL, Fas, CD21, and CD23 and by Western blotting for FasL. FasL mRNA was detected by an exon 4-specific oligonucleotide and Eps tein-Barr virus infection by in situ hybridization far Epstein-Barr virus e arly RNAs (EBER). Western blotting showed soluble and membrane-bound forms of FasL. Immunohistochemistry showed FasL expression in virtually all HRS o f 94% of NS cases and 82% of MC cases. FasL expression did not correlate wi th the Epstein-Barr virus status of the HRS. Low FasL protein expression wa s found in some HRS of LR cases. FasL mRNA. was detected in 39% of NS, 46% of MC, and 33% of LR cases. Seventy percent to 90% of the HRS cells express ed Fas. CD21 immunohistochemistry showed disrupted FDC networks in the tumo r tissue with reduced and virtually absent expression of CD23 and FasL. The se observations suggest that FasL expression in HRS cells and the absence o f FasL in the FDC cluster represent a disturbed microenvironment that may b e involved in the pathogenesis of HL.