TY - JOUR A1 - Geissinger, Eva A1 - Sadler, Petra A1 - Roth, Sabine A1 - Grieb, Tina A1 - Puppe, Bernhard A1 - Mueller, Nora A1 - Reimer, Peter A1 - Vetter-Kauczok, Claudia S. A1 - Wenzel, Joerg A1 - Bonzheim, Irina A1 - Ruediger, Thomas A1 - Mueller-Hermelink, Hans Konrad A1 - Rosenwald, Andreas T1 - Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30(+) T-cell lymphoproliferations N2 - 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 receptoraβ/CD3 complex (CD3γ, δ, ε, ζ), transcription factors regulating T-cell receptor expression (ATF1, ATF2, TCF-1, TCF-1a/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- 1a/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. KW - Medizin KW - systemic and cutaneous CD30+ lymphoproliferations KW - anaplastic large cell lymphoma KW - lymphomatoid papulosis KW - ALCL KW - LyP KW - TCR Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68179 ER - TY - JOUR A1 - Haferkamp, Sebastian A1 - Hesbacher, Sonja A1 - Weyandt, Gerhard A1 - Vetter-Kauczok, Claudia S. A1 - Becker, Jürgen C. A1 - Motschenbacher, Stephanie A1 - Wobser, Marion A1 - Maier, Melissa A1 - Schmid, Corinna P. A1 - Houben, Roland T1 - p53 regulation by TRP2 is not pervasive in melanoma N2 - p53 is a central tumor suppressor protein and its inhibition is believed to be a prerequisite for cancer development. In approximately 50% of all malignancies this is achieved by inactivating mutations in the p53 gene. However, in several cancer entities, including melanoma, p53 mutations are rare. It has been recently proposed that tyrosinase related protein 2 (TRP2), a protein involved in melanin synthesis, may act as suppressor of the p53 pathway in melanoma. To scrutinize this notion we analyzed p53 and TRP2 expression by immunohistochemistry in 172 melanoma tissues and did not find any correlation. Furthermore, we applied three different TRP2 shRNAs to five melanoma cell lines and could not observe a target specific effect of the TRP2 knockdown on either p53 expression nor p53 reporter gene activity. Likewise, ectopic expression of TRP2 in a TRP2 negative melanoma cell line had no impact on p53 expression. In conclusion our data suggest that p53 repression critically controlled by TRP2 is not a general event in melanoma. KW - melanomas KW - melanoma cell KW - cell staining KW - histology KW - reporter genes KW - apoptosis KW - immunohistochemistry techniques KW - tumor suppressor genes Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111396 ER -