TOX, TWIST1, STAT4, and SATB1 protein expressions in early-stage mycosis fungoides

J Cutan Pathol. 2024 Mar;51(3):232-238. doi: 10.1111/cup.14557. Epub 2023 Nov 6.

Abstract

Background: Diagnosis of early mycosis fungoides (eMF) is challenging and often delayed as many of its clinical and histopathologic features may mimic various benign inflammatory dermatoses (BIDs). The products of the thymocyte selection-associated high mobility group box (TOX), twist family BHLH transcription factor 1 (TWIST1), signal transducer and activator of transcription 4 (STAT4), and special AT-rich sequence-binding protein 1 (SATB1) genes function as transcription factors and are involved in the pathogenesis of MF.

Objectives: We aim to determine the diagnostic value of TOX, TWIST1, STAT4, and SATB1 protein expressions in eMF.

Methods: This non-randomized, controlled, prospective analytic study was conducted by performing immunohistochemistry staining with TOX, TWIST1, STAT4, and SATB1 polyclonal antibodies in lesional skin biopsies of eMF and BID patients. Nuclear staining of lymphocytes was compared between eMF and BIDs, and the capacity of these antibodies to predict eMF was determined.

Results: Immunostainings with anti-TWIST1 showed an increase in protein expression (p = 0.003) and showed a decrease with anti-SATB1 antibodies in eMF compared to BIDs (p = 0.005) while anti-TOX and anti-STAT4 antibodies did not exhibit significant differences (p = 0.384; p = 0.150). Receiver operating characteristic analysis showed that immunohistochemical evaluations of TWIST1 and SATB1 protein expressions can differentiate eMF (area under the curve [AUC]: 0.728, 95% confidence interval [CI]: 0.605-0.851, p = 0.002; AUC: 0.686, 95% CI: 0.565-0.807, p = 0.013).

Conclusions: TWIST1 and SATB1 are potential diagnostic markers for the histologic diagnosis of eMF.

Keywords: SATB1; STAT4; TOX; TWIST1; cutaneous T-cell lymphoma; diagnostic biomarker; mycosis fungoides.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Humans
  • Matrix Attachment Region Binding Proteins* / metabolism
  • Mycosis Fungoides* / pathology
  • Nuclear Proteins / metabolism
  • Prospective Studies
  • STAT4 Transcription Factor / metabolism
  • Skin Neoplasms* / pathology
  • Twist-Related Protein 1 / metabolism

Substances

  • Matrix Attachment Region Binding Proteins
  • Nuclear Proteins
  • SATB1 protein, human
  • STAT4 protein, human
  • STAT4 Transcription Factor
  • Twist-Related Protein 1
  • TWIST1 protein, human
  • TOX protein, human