Hodgkin and Reed-Sternberg cells do not carry T-cell receptor gamma gene rearrangements: evidence from single-cell polymerase chain reaction examination

Abstract

Hodgkin and Reed-Sternberg (H&RS) cells are generally accepted to be the neoplastic cells of Hodgkin's disease (HD), even though they represent only a minority of the cellular infiltrate in affected tissues. Recent immunologic studies and Southern blot analyses of DNA extracted from whole lymph node tissue favored, but did not convincingly prove a lymphoid origin of H&RS cells. To detect rearrangements of the T-cell receptor gamma chain (TCR gamma) genes at the single-cell level as an indication of early T-cell lymphoid differentiation, we isolated H&RS cells by micromanipulation from cytospin preparations of fresh biopsy material. TCR gamma chain rearrangement was detected by polymerase chain reaction using four “forward primers” that were constructed corresponding to all four V families and two that were constructed corresponding to all four V families and two “reverse primers” corresponding to consensus sequences of J segments. Rearrangements of all V families in combination with the different J segments were detected in human peripheral blood and tonsillar T cells. Although rearrangements of TCR gamma chain genes were shown in single cells of 10 of 10 T-cell leukemias, no rearrangement of these genes was found in single H&RS cells from 13 consecutive patients with HD. Our results indicate that H&RS cells from the vast majority of cases are not derived from T cells. This finding may have implications for the pathogenesis of HD and the development of more effective treatment regimens.

Rare expression of T-cell markers in classical Hodgkin's lymphoma

“…For comparison, all other studies that focused on single Hodgkin's and Reed-Sternberg cell analysis for clonal T-cell receptor gene rearrangements were performed on cells isolated from frozen tissue. 23,27,29 Nevertheless, the number of our cases with genotypic evidence of possible T-cell origin from among all phenotypically T-cell marker-positive classical Hodgkin's lymphomas (two of 12) is in accord with the report of Seitz et al 27 (two of 13). Our findings indicate that most Tcell antigen-positive classical Hodgkin's lymphomas aberrantly express these proteins, and only very few cases are of possible T-cell origin.…”

“…[12][13][14][15][16][17]19,[22][23][24]27,28 In a small number of cases, the expression of T-cell markers was corroborated by analysis of the T-cell receptor genes for clonal rearrangements on microdissected single Hodgkin's and Reed-Sternberg cells. 23,27,29 However, only three cases have been shown thus far to be of unequivocal T-cell origin. 23,27 Moreover, there are controversial data on clonal relationships between Hodgkin's and Reed-Sternberg cells and T cells in patients with composite classical Hodgkin's lymphoma/T-non-Hodgkin's lymphoma, 20,30 with most cases being of different clonal origin.…”

Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma

“…In addition, recent results obtained by others indicate B cell derivation of H/RS cells in 24 out of 25 cases of cHD 20. On the other hand, in a nonselected collection of 13 cases of primary cHD, Daus and colleagues did not detect clonal TCR-γ gene rearrangements in micromanipulated H/RS cells from any of these cases 21. Therefore, these data collectively indicate that cHD represents a homogenous entity as a B cell lymphoma.…”

The Reed–Sternberg cell in classical Hodgkin's disease

“…There has been only one single cell study examining TCR gamma gene rearrangement and no rearrangement was detected in 13 cases examined, 69 but this same group also reported no IgH rearrangement in H/RS cells in a previous study. 61…”