Expression of Paraoxonase-2 in Different Stages of Cutaneous T Cell Lymphoma: Is It a Potential Biomarker for Aggressiveness?

Abstract

Introduction: Paraoxonase 2 (PON2) is an intracellular membrane protein that belong to the PON gene family. This enzyme exerting a crucial role against production of reactive oxygen species within mithochondrial respiratory chain. Some reports provided clinical evidence for a link between PON2 and different types of malignancies and recently a growing attention has been focused on exploring the role of PON2 in cancer. Moreover, in contrast to solid tumors, a low expression levels of PON2 protein were detected in hematological malignancies like acute myeloid leukemia and B-cell lymphomas. The aim of this study was to investigate the role of PON2 in the cutaneous T cells Lymphoma (CTCL).Methods: We performed an immunohistochemistry analysis of PON2 protein expression at various stages CTCL. We analyzed PON2 protein using skin biopsies from stage I (n= 3) and stage II (n= 6) Mycosis Fungoides (MF) and stage III/IV (n= 5) erythrodermic MF/Sézary Syndrome (SS) and control (n=6) tissues. Values were expressed as percentage of PON2-positive staining cells, whereas the intensity of PON2 positivity was semi-quantitatively scored from negative to -/+/+++. Subsequent statistical analysis was carried out to explore the existence of correlations between intra-tumor enzyme level and clinical-pathological features at diagnosis.Results: In our preliminary study, results showed PON2 down-expression in SS compared to controls. Among CTCL, we found significant differences in enzyme levels between MF and erythrodermic MF/SS; in fact, PON2 expression was higher in patients with not erythrodermic MF compared to patients with erythrodermic MF/SS. (Table I) Moreover, we found no significant differences in enzyme levels between MF patients and controls.Conclusion: Our study is the first to demonstrate downregulation of PON2 intra-tumoral in SS patients while protein levels were higher in stage I and II MF patients. These findings seem to suggest that PON2 expression levels could be negatively related with tumor aggressiveness in CTCL: an interesting phenomenon where PON2 is upregulated in the early stages and downregulated in the late stages of CTCL. Further, in vitro studies are needed to clarify the mechanism related to PON2 expression. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.