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

• Published in: Haematologica (Roma) 2010-10, Vol.95 (10), p.1697-1704
• Main Authors: Geissinger, Eva, Sadler, Petra, Roth, Sabine, Grieb, Tina, Puppe, Bernhard, Müller, Nora, Reimer, Peter, Vetter-Kauczok, Claudia S, Wenzel, Jörg, Bonzheim, Irina, Rüdiger, Thomas, Müller-Hermelink, Hans Konrad, Rosenwald, Andreas
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomarkers, Tumor - analysis; CD3 Complex - analysis; Dermatology; Hematologic and hematopoietic diseases; Humans; Ki-1 Antigen - analysis; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Large-Cell, Anaplastic - diagnosis; Lymphoma, T-Cell, Cutaneous - diagnosis; Medical sciences; Original; Receptors, Antigen, T-Cell - analysis; Skin involvement in other diseases. Miscellaneous. General aspects
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2009.021428

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. 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. 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. 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.