Cancer Res Treat.  2008 Dec;40(4):197-201.

Altered Expression of Smad Proteins in T or NK-cell Lymphomas

• Go JH

Abstract

PURPOSE: Smad proteins mediate cellular signaling through the transforming growth factor-beta family (TGF-beta s). Smads 2 and 3 transmit signals from TGF-beta, and Smad4 is a common mediator, as well. However, little is known concerning the expression patterns of Smads in lymphoid tissue.
MATERIALS AND METHODS
Immunohistochemistry for Smad3 and Smad4 was performed on paraffin-embedded tissue sections collected from 26 T- or NK-cell lymphomas.
RESULTS
Nearly all cells in germinal centers were positive for Smad3, and more than 50% of paracortical cells were positive for Smad3 in reactive lymphoid tissue. When Smad4 immunostaining was conducted, nearly all the cells in the germinal centers showed diffuse cytoplasmic staining, and most of them exhibited nuclear positivity, as well. In addition, more than 50% of the cells in the paracortex were positive for Smad4. Furthermore, the Smad3 staining pattern was preserved in all malignant lymphomas, but four of these cases (15%) exhibited decreased expression of Smad4. All lymphoblastic lymphomas showed strong positivity in most of tumor cells, but one unspecified peripheral lymphoma, two nasal NK/T cell lymphomas, and one anaplastic large cell lymphoma were negative for Smad4.
CONCLUSIONS
These results suggest that TGF-beta-specific Smads may be actively involved in signal transduction in lymphoid organs and that Smad-mediated TGF-beta signaling pathways are operative in malignant lymphoma. In addition, loss of Smad4 expression might be associated with development of some T-cell lymphomas.

Keyword

Smad proteins; T lymphocytes; Lymphoma; Etiology

MeSH Terms

Cytoplasm
Germinal Center
Humans
Immunohistochemistry
Lymphoid Tissue
Lymphoma
Lymphoma, Large-Cell, Anaplastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Signal Transduction
Smad Proteins
T-Lymphocytes
Transforming Growth Factor beta
Smad Proteins
Transforming Growth Factor beta

Figure

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  Fig. 1 When Smad3 immunostaining was conducted, more than 50% of the thymocytes showed strong nuclear staining (A), and more than 50% of the paracortical cells were positive with moderate staining intensity (B). When Smad4 immunostaining was conducted, nearly all of the thymocytes showed strong to moderate nuclear staining (C), and more than 50% of the cells in the paracortex were positive, with moderate staining intensity (D).

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  Fig. 2 When the T-cell lymphomas were evaluated, all of the cases were strongly positive for Smad3.

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  Fig. 3 Twenty-one T-cell lymphomas were moderately to strongly positive for Smad4, and four cases (15%) were negative for Smad4.

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