P53 EXPRESSION IN LANGERHANS CELL HISTIOCYTOSIS

Purpose: Langerhans cell histiocytosis (LCH) is a disorder of unknown etiology involving the proliferation and accumulation of cells with th e phenotype of a bone marrow-derived antigen-presenting cell of the sk in, the Langerhans cell. We have studied p53 expresssion, an element i n the control of cell proliferation, to determine whether it plays a r ole 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 immunohistoch emistry, and p53 gene mutation by the single strand conformation polym orphism (SSCP) technique. Results: p53 protein expression was detected in all 10 LCH biopsy specimens examined. It was restricted to Langerh ans cells (LCH cells), absent from adjacent cells, and localized to th e cell nuclei. No mutations of the p53 gene were detected, nor was the re abnormal expression of the p53 binding protein, mdm2. Conclusions: p53 is readily detectable in LCH cells but not in normal cells. This i s either caused by an unusual mechanism (given the absence of mutation s in the p53 gene and of mdm2 expression in LCH cells) or by overexpre ssion or posttranslational changes of normal p53 in response to an as yet unidentified cellular stress, Stabilization and inactivation of p5 3 could lead to the uncontrolled proliferation of LCH cells, or the ab normality could lead to the induction of programmed cell death.