Transforming growth factor β1 messenger RNA in Reed-Sternberg cells in nodular sclerosing Hodgkin's disease

Abstract

Aims - To determine the cellular origin of the most potent cytokine present in Hodgkin's disease, transforming growth factor (TGF) β, the polycellular population of Hodgkin's tissue was studied using in situ hybridisation. Methods - A biotin labelled oligo-complementary DNA (cDNA) was constructed according to the previously determined sequence for TGFβ1 cDNA. Forty three frozen and paraffin wax embedded tissue samples replaced by Hodgkin's disease or non-Hodgkin's lymphoma, three Reed-Sternberg cell lines, one Ki1 positive lymphoma cell line, and an epithelial cell line were studied for expression of TGFβ1 messenger RNA (mRNA) as well as secretion of the TGFβ1 protein and expression of the CD30 epitope. Results - The results obtained with the 24 frozen tissue samples confirmed that the TGFβ antigen is found predominantly in the nodular sclerosing Hodgkin's disease (NSHD) subtype. Nineteen paraffin wax embedded tissue samples were used to measure the simultaneous expression of CD30 and TGFβ1 mRNA. The latter was found in eight of eight NSHD samples, two of six mixed cellularity samples, and two of five non-Hodgkin's lymphoma samples. No evidence of fibroblast expression of TGFβ1 mRNA was noted. Conclusions - Activated lymphocytes in NSHD express TGFβ1 mRNA, but binucleate Reed-Sternberg cells and mononuclear Hodgkin's cells are the primary sources of activated TGFβ in Hodgkin's disease.