Role of chromatin assembly factor-1/p60 and poly [ADP-ribose] polymerase 1 in mycosis fungoides

Virchows Arch. 2021 May;478(5):961-968. doi: 10.1007/s00428-020-02952-z. Epub 2020 Oct 24.

Abstract

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. In the majority of patients, the disease has a slow evolution and a protracted course; however, a subset of patients shows poor oncologic outcomes. Unfortunately, there are no reliable prognostic markers for MF, and the currently available treatments are only effective in a minority of patients. This study aimed to evaluate the expression and clinical significance of PARP-1 and CAF-1/p60 in MF. Sixty-four MF representatives of the different stages of disease were assessed by immunohistochemistry for PARP-1 and CAF-1/p60. The association of PARP-1 and CAF-1/p60 with the MF stage and outcome was assessed by using Fisher's exact test and Kaplan-Meier survival analysis with the Log-rank test; a p value < 0.05 was considered significant. PARP-1 was overexpressed in 57.9% of MF and was significantly associated with a MF stage > II (p = 0.034) but not with the risk of death (p = 0.237). CAF-1/p60 was overexpressed in 26.8% of MF and was significantly associated with decreased overall survival (p < 0.001) but not with the MF stage (p = 1). A significant association was found between PARP-1 overexpression and CAF-1/p60 overexpression (p = 0.0025). Simultaneous overexpression of PARP-1 and CAF-1/p60 was significantly associated with decreased overall survival (p < 0.001), although less strongly than CAF-1/p60 alone (χ2 = 14.916 vs 21.729, respectively). In MF, PARP-1 is overexpressed in advanced stages, while CAF-1/p60 is overexpressed in the cases with shorter overall survival, appearing as a significant prognostic marker. A role for PARP-1 inhibitors and anti-CAF-1/p60 targeted therapy may be reasonably hypothesized in MF.

Keywords: Chromatin assembly factor-1; Cutaneous lymphoma; Mycosis fungoides; Poly [ADP-ribose] polymerase 1; Prognosis.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Chromatin Assembly Factor-1 / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Italy
  • Male
  • Middle Aged
  • Mycosis Fungoides / enzymology*
  • Mycosis Fungoides / mortality
  • Mycosis Fungoides / pathology
  • Mycosis Fungoides / therapy
  • Neoplasm Staging
  • Poly (ADP-Ribose) Polymerase-1 / analysis*
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Skin Neoplasms / enzymology*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • CHAF1A protein, human
  • Chromatin Assembly Factor-1
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1