Supplementary Tables 1-4, Figure 1. Supplementary Table 1. Primers used for RT-PCR experiments. Supplementary Table 2. Detailed description of the 52 genes that fit into the three signature pattern expression model and their putative functions in CTCL and other malignancies. Supplementary Table 3. Multivariate analysis of patient characteristics that are associated with clinical disease progression. Supplementary Table 4. Description of genes that are able to distinguish CTCL from benign dermatoses and their putative roles in CTCL and other malignancies. Supplementary Figure 1. A. WIF1 (Wnt Inhibitory Factor 1) gene is expressed in normal skin and CTCL lesional skin in a subset of patients. B. Correlation of WIF1 expression in CTCL patients with disease progression. Kaplan-Meier analysis documents that loss of WIF1 expression is associated with poor CTCL disease progression (left panel, p=0.002). Disease progression is defined as a progression to a higher clinical stage and/or death. Loss of WIF1 is also associated with poor cancer specific survival (right panel, p=0.012).
ARTICLE ABSTRACT
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.
