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

Massimo Mascolo,Marco Picardi,Alessandro Pileri,Antonello Baldo,Fabrizio Pane,Claudio Agostinelli,Clara Bertuzzi,Silvia Varricchio,Antonio Travaglino,Elena Sabattini,Stefania Staibano,Daniela Russo

doi:10.1007/s00428-020-02952-z

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.

Highlights

Mycosis fungoides (MF) is the most common type of primary cutaneous lymphoma, accounting for about 50% of cases [1, 2]
poly [ADP-ribose] polymerase 1 (PARP-1) resulted overexpressed in 33 cases (57.9%), while CAF-1/p60 was overexpressed in 15 cases (26.8%) (Figs. 1, 2, and 3)
Among the 12 cases with large cell transformation, PARP-1 and CAF-1/p60 immunostaining was successful in 11/12 cases, out of which (90.9%) showed PARP-1 overexpression and 4 (36.4%) showed CAF-1/p60 overexpression; remarkably, considering only the large cells, both PARP-1 and CAF-1/p-60 were overexpressed in all cases (100%)

Summary

Introduction

Mycosis fungoides (MF) is the most common type of primary cutaneous lymphoma, accounting for about 50% of cases [1, 2]. Few MF cases may undergo large cell transformation, characterized by an aggressive clinical course and a median survival of less than 2 years [11]. As it combines skindirected and systemic therapies [12]. Targeted therapies achieve a complete response in less than half of patients, while conventional chemotherapy is associated with shortlived responses and worse overall outcomes [13,14,15]. The only potential cure for MF is traditional non-myeloablative allogeneic stem cell transplantation, which an overall survival rate of 46% at 5 years [15]

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