Cutaneous T-Cell Lymphomas (CTCL) are rare, but potentially devastating malignancies, whose pathogenesis remains poorly elucidated. Unfortunately, currently it is not possible to predict based on the available criteria in which patients the cancer will progress and which patients will experience an indolent disease course. Furthermore, at early stages this malignancy often masquerades as psoriasis, chronic eczema or other benign inflammatory dermatoses. As a result, it takes on average 6 y to diagnose this lymphoma since its initial presentation. In this study, we performed transcription expression profiling using TruSeq targeted RNA gene expression on 181 fresh and formalin-fixed and paraffin-embedded (FFPE) skin samples from CTCL patients and patients affected by benign inflammatory dermatoses that often mimic CTCL clinically and on histology (e.g., psoriasis, chronic eczema, etc.) We also analyzed multiple longitudinal biopsies that were obtained from the same patients over time. Our results underscore significant molecular heterogeneity with respect to gene expression between different patients and even within the same patients over time. Our study also confirmed TOX, FYB, LEF1, CCR4, ITK, EED, POU2AF, IL26, STAT5, BLK, GTSF1 and PSORS1C2 genes as being differentially expressed between CTCL and benign skin biopsies. In addition, we found that differential expression for a subset of these markers (e.g., TOX, FYB, GTSF1 and CCR4) may be useful in prognosticating this disease. This research, combined with other molecular analyses, prepares the foundation for the development of personalized molecular approach toward diagnosis and management of CTCL.

Purpose: Although many patients with mycosis fungoides presenting with stage I disease enjoy an indolent disease course and normal life expectancy, about 15% to 20% of them progress to higher stages and most ultimately succumb to their disease. Currently, it is not possible to predict which patients will progress and which patients will have a stable disease. Previously, we conducted microarray analyses with RT-PCR validation of gene expression in biopsy specimens from 60 patients with stage I–IV cutaneous T-cell lymphoma (CTCL), identified three distinct clusters based upon transcription profile, and correlated our molecular findings with 6 years of clinical follow-up. Experimental Design: We test by RT-PCR within our prediction model the expression of about 240 genes that were previously reported to play an important role in CTCL carcinogenesis. We further extend the clinical follow-up of our patients to 11 years. We compare the expression of selected genes between mycosis fungoides/Sézary syndrome and benign inflammatory dermatoses that often mimic this cancer. Results: Our findings demonstrate that 52 of the about 240 genes can be classified into cluster 1–3 expression patterns and such expression is consistent with their suggested biologic roles. Moreover, we determined that 17 genes (CCL18, CCL26, FYB, T3JAM, MMP12, LEF1, LCK, ITK, GNLY, IL2RA, IL26, IL22, CCR4, GTSF1, SYCP1, STAT5A, and TOX) are able to both identify patients who are at risk of progression and also distinguish mycosis fungoides/Sézary syndrome from benign mimickers. Conclusions: This study, combined with other gene expression analyses, prepares the foundation for the development of personalized molecular approach toward diagnosis and treatment of CTCL. Clin Cancer Res; 21(12); 2820–9. ©2015 AACR.

Deregulation of STAT signaling has been implicated in the pathogenesis for a variety of cancers, including CTCL. Recent reports indicate that loss of STAT4 expression is an important prognostic marker for CTCL progression and is associated with the acquisition of T helper 2 cell phenotype by malignant cells. However, little is known about the molecular mechanism behind the downregulation of STAT4 in this cancer. In the current work we test the expression of STAT4 and STAT6 via RT-PCR and/or Western Blot in CTCL lesional skin samples and in immortalized patient-derived cell lines. In these malignant cell lines we correlate the expression of STAT4 and STAT6 with the T helper (Th) phenotype markers and test the effect of Histone Deacetylase (HDAC) inhibitors and siRNA-mediated knock down of miR-155 on STAT4 expression. Our findings demonstrate that STAT4 expression correlates with Th1 phenotype, while STAT6 is associated with the Th2 phenotype. Our results further document that STAT4 and STAT6 genes are inve...