Expression Pattern of Smad Proteins in Diffuse Large B-cell Lymphomas

Go, Jai Hyang

Abstract

BACKGROUND: Smad proteins mediate the cellular signaling from members of transforming growth factor-beta family (TGF-beta s). Smads 2 and 3 transmit signals from TGF-beta and activin, and Smads 1, 5, and 8 transmit signals from the bone morphogenetic protein. Smad4 is known to be a common mediator of both pathways, yet little is known about the expression pattern of Smad proteins in normal lymphoid tissue and malignant lymphoma.
METHODS
Immunohistochemistry was performed for Smad3 and Smad4 on the paraffin-embedded tissue sections from 32 cases of diffuse large B-cell lymphomas.
RESULTS
In reactive lymphoid tissue, nearly all cells of the germinal centers were positive for Smad3 and more than 50% of paracortical cells were positive for Smad3. For Smad4 immunostaining, nearly all cells of the germinal centers showed diffuse cytoplasmic staining, and most of them revealed nuclear positivity as well. Most of the cells in the paracortex regions were positive for Smad4. For the malignant lymphomas, all the cases were positive for Smad3, but 26 cases were positive for Smad4 and 6 cases (19%) were negative for Smad4.
CONCLUSIONS
These results suggest that TGF-beta-specific Smads may be actively involved for signal transduction in lymphoid organs, and the TGF-beta signaling pathway through Smads is operative in malignant lymphoma. The loss of Smad4 expression might be associated with development of some diffuse large B-cell lymphomas.