Transcriptional Profiles Predict Disease Outcome in Patients with Cutaneous T-Cell Lymphoma

Abstract

Purpose: Average survival of cutaneous T-cell lymphoma (CTCL) is associated with clinical stage at diagnosis, where stage I has a favorable survival prognosis, whereas patients with more advanced stages succumb to their disease within 5 years. Although the majority of patients present with an early-stage CTCL, 15% to 20% of them will inevitably progress. Current state-of-the-art clinical criteria cannot identify individuals with stage I disease who are at risk of progression. The purpose of the current work is to gain novel molecular insight into the pathophysiology of CTCL to be able to identify patients with poor versus favorable prognosis. Our previous work used microarray analysis of skin biopsies from 62 CTCL patients to perform an unsupervised analysis of gene expression, which revealed three distinct transcription profile clusters.Experimental Design: In the present study, we used reverse transcription-PCR to confirm gene expression levels for a subset of representative genes in each cluster. We also performed a Kaplan-Meier analysis of survival and disease progression based on the 6 years of clinical follow-up.Results: Our reverse transcription-PCR results confirmed the upregulation of representative genes for each cluster, whereas clinical analysis documents that all stage I cases that progressed to stage II and beyond were in poor and intermediate prognosis clusters 1 and 3 and none were in favorable prognosis cluster 2. This analysis also identified certain genes that were preferentially expressed in favorable (e.g.,

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Shin et al performed a gene expression profiling analysis on lesional skin biopsy specimens obtained from 62 CTCL patients and identified three distinct gene expression clusters that were prognostically important [47], that were later confirmed by RT-PCR analysis [195]. The first cluster was associated with the upregulation of genes involved in T-cell activation, homing and tumor necrosis factor (TNF) signaling.…”

Ectopic expression of embryonic stem cell and other developmental genes in cutaneous T-cell lymphoma

“…The historic cohort of patients from Boston (n D 60) that was initially reported in 2007, 4 was at the heart of extensive research that led to multiple publications in the field. 3,4,13,14,16,53,57,58 The biopsy samples analyzed in this report are the same samples that were analyzed in previous studies. 3,4,13,14,16,57,58 Similarly, volunteers with normal healthy skin (N D 5) and benign inflammatory dermatoses (N D 19) were recruited from the outpatient dermatology clinic of the University of British Columbia (Vancouver, Canada) with informed consent.…”

“…3,13,14 Briefly, RT-PCR was performed utilizing the obtained cDNA from patients and cell lines using iScript RT-PCR mix (Bio-Rad, Catalog #170-8893) on Bio-Rad iCycler (Bio-Rad, Catalog # 185-5201). Primer pair sequences for tested genes and control housekeeping genes are listed in Table S2.…”

“…2 Multiple studies attempted to clarify the genetic multistep carcinogenesis of CTCL. [3][4][5][6] In addition, several studies identified recurrent chromosomal aberrations in MF/SS. [7][8][9][10][11][12] While much research is focused on investigation of known oncogenes and tumor suppressor genes in CTCL, 6,[13][14][15] recent reports suggest that it is also important to look for genes that could be erroneously expressed in this cancer.…”

New molecular insights into peripheral T cell lymphomas

“…Unfortunately, most of these studies (15)(16)(17)(18)(19) provided very little information on the histogenesis of PTCLs, although they focused on several categories, from mycosis fungoides (MF) to cutaneous TCLs, AITL, PTCL-NOSs, and ALK + and ALK -ALCL. This was related to limitations in the study design and/or technologies employed.…”