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


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.
Geissinger
Eva
E
Institute of Pathology, University of Wuerzburg, Josef Schneider-Strasse 2, Wuerzburg, Germany. geissinger@mail.uniwuerzburg.de
Sadler
Petra
P
Roth
Sabine
S
Grieb
Tina
T
Puppe
Bernhard
B
Müller
Nora
N
Reimer
Peter
P
Vetter-Kauczok
Claudia S
CS
Wenzel
Jörg
J
Bonzheim
Irina
I
Rüdiger
Thomas
T
Müller-Hermelink
Hans Konrad
HK
Rosenwald
Andreas
A
D014408:Biomarkers, Tumor / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis*; D006801:Humans; D017730:Ki-1 Antigen / Q000032:analysis*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000175:diagnosis*; D016410:Lymphoma, T-Cell, Cutaneous / Q000175:diagnosis*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*
D014408:Biomarkers, Tumor; D017252:CD3 Complex; D017730:Ki-1 Antigen; D011948:Receptors, Antigen, T-Cell