title: Molecular markers of early-stage mycosis fungoides.
abstract: The lack of a specific marker differentiating early mycosis fungoides (eMF) from benign inflammatory dermatitis presents significant difficulties in the assessment and management of suspected MF patients, which often leads to delayed diagnosis and improper medical approaches. To address this, an investigation was carried out to characterize positive identification markers for eMF by comparing eMF lesions with healthy skin and benign inflammatory dermatitis, using high-throughput genomic transcription profiling. A total of 349 genes were differentially expressed in eMF lesions compared with normal skin. These genes belong to pathways associated with inflammation, immune activation, and apoptosis regulation. Most of them (N=330) also demonstrated significant upregulation in chronic dermatitis, making them nonideal markers for eMF. Among them, 19 genes with specific enrichment in eMF lesions were identified that showed no significant upregulation in chronic dermatitis. Two of them, TOX and PDCD1, showed high discrimination power between eMF lesions and biopsies from benign dermatitis by RNA expression. Furthermore, TOX demonstrated highly specific staining of MF cells in eMF skin biopsies in immunohistochemistry and immunofluorescence, including the early epidermotropic cells in Pautrier's microabscesses. This study demonstrates the potential of eMF-enriched genes, especially TOX, as molecular markers for histological diagnosis of eMF, which currently is a major diagnostic challenge.
authors.affiliation: Molecular Medicine Laboratory and Chieng Genomics Centre, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Richard
authors.initials: R
authors.lastname: Yu
authors.forename: Yuanshen
authors.initials: Y
authors.lastname: Huang
authors.forename: Mingwan
authors.initials: M
authors.lastname: Su
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiao
authors.forename: Magdalena
authors.initials: M
authors.lastname: Martinka
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dutz
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002908:Chronic Disease; D003872:Dermatitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D006609:High Mobility Group Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C558851:TOX protein, human