TOX expression and role in CTCL
Background Cutaneous T‐cell lymphomas (CTCL) are skin malignancies including mycosis fungoides (MF) and CD30+ lymphoproliferative disorders (LPD). In early disease, CTCL can be difficult to diagnose, especially in MF for which there is no reliable diagnostic marker. MF/CTCL have increased expression...
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| Published in: | Journal of the European Academy of Dermatology and Venereology Vol. 30; no. 9; pp. 1497 - 1502 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
Blackwell Publishing Ltd
01-09-2016
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Background
Cutaneous T‐cell lymphomas (CTCL) are skin malignancies including mycosis fungoides (MF) and CD30+ lymphoproliferative disorders (LPD). In early disease, CTCL can be difficult to diagnose, especially in MF for which there is no reliable diagnostic marker. MF/CTCL have increased expression of thymocyte selection‐associated HMG box protein (TOX). Although TOX has been proposed to be a diagnostic marker for MF, further validation studies are needed. Moreover, it is unclear what drives TOX expression or its role in MF/CTCL.
Objective
We hypothesize evaluation of TOX levels across a spectrum of CTCL, including MF precursor (large plaque parapsoriasis, LPP), will help elucidate the implications of altered TOX expression.
Materials and Methods
TOX staining was performed in MF, CD30+ LPD, LPP as well as benign inflammatory dermatoses (BID) and normal skin (NS). CTCL cell lines were utilized to evaluate the regulation of TOX.
Results
Positive TOX expression was identified in 73.6% of MF cases and in 31.6% of BID/NS. TOX had a positive predictive value (PPV) for MF of 86.7% and a negative predictive value (NPV) of 48.1%. TOX expression in MF was detected more commonly in Black patients (P = 0.015) and less commonly in transformed MF (P = 0.045). LPP had positive TOX staining in 70.0%. In CTCL cells, GATA3 knockdown decreased TOX mRNA and protein expression. TOX expression also decreased in the presence of CTCL therapeutics.
Conclusion
Our data indicate that TOX is useful as a diagnostic marker in MF. Moreover, TOX expression was evident in LPP, indicating it may have a previously unappreciated role in the development of MF. Finally, our data suggest that GATA3 regulates TOX, revealing insight into TOX regulation. |
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| Bibliography: | Vanderbilt Department of Medicine/Dermatology ArticleID:JDV13651 Vanderbilt Cutaneous Lymphoma Fund ark:/67375/WNG-5MKQFPBD-7 Dermatology Foundation Physician-Scientist Career Development Award Hematology Helping Hands Fund - No. R01CA148950 NIH - No. K12CA090625; No. UL1TR000445 McDaniel Gift Fund istex:013EFE066C6AEA3657B1A0E3CA4DE42B89FC34CC Funding Sources Conflicts of Interest This work was supported by Dermatology Foundation Physician‐Scientist Career Development Award (LYM), the NIH supported Vanderbilt Clinical Oncology Research Career Development Program (K12CA090625), NIH (UL1TR000445), Hematology Helping Hands Fund (CME and LYM), R01CA148950 (CME), and the Vanderbilt Department of Medicine/Dermatology, the McDaniel Gift Fund, the Vanderbilt Cutaneous Lymphoma Fund and an anonymous donor. None to disclose. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 co-first authors |
| ISSN: | 0926-9959 1468-3083 |
| DOI: | 10.1111/jdv.13651 |