Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30+ T-cell lymphoproliferations.

Abstract

BACKGROUND:

CD30(+) T-cell lymphoproliferations comprise a spectrum of clinically heterogeneous entities, including systemic anaplastic large cell lymphomas (ALK(-) and ALK(+)) and primary cutaneous CD30(+) T-cell lymphoproliferative disorders. While all these entities are characterized by proliferation of highly atypical, anaplastic CD30(+) T cells, the expression of T-cell specific antigens in the tumor cells is not consistently detectable.

DESIGN AND METHODS:

We evaluated biopsies from 19 patients with primary cutaneous CD30(+) lymphoproliferative disorders, 38 with ALK(-) and 33 with ALK(+) systemic anaplastic large cell lymphoma. The biopsies were examined for the expression of T-cell receptorαβ/CD3 complex (CD3γ, δ, ε, ζ), transcription factors regulating T-cell receptor expression (ATF1, ATF2, TCF-1, TCF-1α/LEF-1, Ets1), and molecules of T-cell receptor-associated signaling cascades (Lck, ZAP-70, LAT, bcl-10, Carma1, NFATc1, c-Jun, c-Fos, Syk) using immunohistochemistry.

RESULTS:

In comparison to the pattern in 20 peripheral T-cell lymphomas, not otherwise specified, we detected a highly disturbed expression of the T-cell receptor/CD3 complex, TCF-1, TCF-1α/LEF-1, Lck, ZAP-70, LAT, NFATc1, c-Jun, c-Fos and Syk in most of the systemic anaplastic large cell lymphomas. In addition, primary cutaneous CD30(+) lymphoproliferative disorders showed such a similar expression pattern to that of systemic anaplastic large cell lymphomas, that none of the markers we investigated can reliably distinguish between these CD30(+) T-cell lymphoproliferations.

CONCLUSIONS:

Severely altered expression of the T-cell receptor/CD3 complex, T-cell receptor-associated transcription factors and signal transduction molecules is a common characteristic of systemic and cutaneous CD30(+) lymphoproliferations, although the clinical behavior of these entities is very different. Since peripheral T-cell lymphomas, not otherwise specified retain the full expression program required for functioning T-cell receptor signaling, the differential expression of a subset of these markers might be of diagnostic utility in distinguishing peripheral T-cell lymphomas, not otherwise specified from the entire group of CD30(+) lymphoproliferations.

• Authors: Eva Geissinger, Petra Sadler, Sabine Roth, Tina Grieb, Bernhard Puppe, Nora Müller, Peter Reimer, Claudia S Vetter-Kauczok, Jörg Wenzel, Irina Bonzheim, Thomas Rüdiger, Hans Konrad Müller-Hermelink, Andreas Rosenwald
• Journal: Haematologica (Haematologica) Vol. 95 Issue 10 Pg. 1697-704 (Oct 2010) ISSN: 1592-8721 [Electronic] Italy
• PMID: 20511667 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• CD3 Complex
• Ki-1 Antigen
• Receptors, Antigen, T-Cell

Topics

• Biomarkers, Tumor (analysis)
• CD3 Complex (analysis)
• Humans
• Ki-1 Antigen (analysis)
• Lymphoma, Large-Cell, Anaplastic (diagnosis)
• Lymphoma, T-Cell, Cutaneous (diagnosis)
• Receptors, Antigen, T-Cell (analysis)