Sensitive and Specific Detection of Gamma T-Cell Receptor in Paraffin-Embedded T-Cell Lymphomas
GBW Wertheim, M Roullet, D Jones, KH Young, S Li, H Wu, JK Choi. Hospital of the Univ. of Penn, Phila, PA; Children's Hospital of Phila, Phila, PA; Norfolk General Hospital, Norfolk, VA; Univ of Texas MD Anderson Cancer Center, Houston, TX; Univ. of Wisconsin, Madison, WI; Fox Chase Cancer Center, Phila, PA; Emory Univ. School of Med., Atlanta, GA
Background: The γδ T-cell receptor (TCR-γδ) is expressed in 5% of normal T cells and in some T-cell lymphoblastic leukemia/lymphomas; extranodal NK/T cell lymphomas, nasal type; hepatosplenic T-cell lymphomas and primary cutaneous T cell lymphomas. Expression of TCR-γδ in cutaneous T cell lymphomas is associated with worse outcomes compared to TCR-αβ-expressing tumors with similar histology. Currently, detection of the TCR-γδ is restricted to immunohistochemistry on frozen tissue or flow cytometry on fresh samples. If direct detection cannot be performed, TCR-γδ expression is assumed if T cells are negative for TCR-αβ and other T cell markers (i.e. CD4/CD8). Recently, we identified a new antibody that stains TCRγ in paraffin sections (AJCP, 2009). We now address the utility of this antibody for subtyping T-cell lymphomas.
Design: Sections from 62 T-cell lymphomas were obtained; 22 were positive for TCR-γδ expression, determined by flow cytometry or frozen section immunohistochemistry. Paraffin immunohistochemistry was performed using antibodies to TCRβ (βF1), TCRγ, and CD3.
Results: We found TCR-γ-positivity in 21 of 22 TCR-γδ proven cases (95% sensitivity). None of these samples showed βF1 staining. Of the 28 βF1-positive cases, 24 were negative for TCRγ staining (86% specificity). In nine cases examined, neither βF1 nor TCRγ expression was detected. Three were TCRγ-positive, βF1-negative, but did not have confirmatory studies.
Conclusions: We characterized the sensitivity and specificity of a TCRγ antibody in paraffin sections of T-cell lymphomas. Used in conjuction with other T-cell antibodies, this method can be used to assess TCR status accurately. Given the high sensitivity of our method and the multiple cases that lack TCRγ and βF1 expression, our results challenge the assumption that βF1-negativity implies a TCR-γδ phenotype. Finally, the four cases in which both βF1 and TCRγ stains are positive may represent off-target interactions, or aberrant dual expression of TCRβ and TCRγ.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 194, Monday Morning