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 and 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., and) 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 While many Mycosis Fungoides (MF) patients presenting with stage I disease enjoy an indolent disease course and normal life expectancy, about 15-20% of them progress to higher stages, and most ultimately succumb to their disease. Currently, it's 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 stage I-IV CTCL patients, 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 ∼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 MF/Sézary Sydrome and benign inflammatory dermatoses that often mimic this cancer. Results Our findings demonstrate that 52 out of the ∼240 genes can be classified into cluster 1-3 expression patterns and such expression is consistent with their suggested biological roles. Moreover, we determined that 17 genes (CCL18, CCL26, FYB, T3JAM, MMP12, LEF1, LCK, ITK, GNLY, IL2RA, IL-26, IL-22, CCR4, GTSF1, SYCP1, STAT5A, TOX) are able to both identify patients who are at risk of progression and also distinguish MF/SS from benign mimickers. Conclusions This study, combined with other gene expression analyses, prepares the foundation for the development of personalized molecular approach towards diagnosis and treatment of CTCL.

The current results provide a comprehensive analysis of CTCL burden in Canada and highlight several important areas of geographic case clustering. These findings argue that industrial exposures may play an important role in promoting CTCL pathogenesis. Cancer 2017;123:3550-67. © 2017 American Cancer Society.