p53 expression in Langerhans cell histiocytosis

Abstract

Purpose: Langerhans cell histiocytosis (LCH) is a disorder of unknown etiology involving the proliferation and accumulation of cells with the phenotype of a bone marrow-derived antigen-presenting cell of the skin, the Langerhans cell. We have studied p53 expression, an element in the control of cell proliferation, to determine whether it plays a role in the pathogenesis of LCH.

Patients and methods: LCH lesions from 10 patients with either localized (n = 5) or multisystem disease (n = 5) were studied. p53 protein expression was assessed by immunohistochemistry, and p53 gene mutation by the single strand conformation polymorphism (SSCP) technique.

Results: p53 protein expression was detected in all 10 LCH biopsy specimens examined. It was restricted to Langerhans cells (LCH cells), absent from adjacent cells, and localized to the cell nuclei. No mutations of the p53 gene were detected, nor was there abnormal expression of the p53 binding protein, mdm2.

Conclusions: p53 is readily detectable in LCH cells but not in normal cells. This is either caused by an unusual mechanism (given the absence of mutations in the p53 gene and of mdm2 expression in LCH cells) or by overexpression or posttranslational changes of normal p53 in response to an as yet unidentified cellular stress. Stabilization and inactivation of p53 could lead to the uncontrolled proliferation of LCH cells, or the abnormality could lead to the induction of programmed cell death.