Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis. Issue 11 (November 2014)

• Record Type: Journal Article
• Authors: Chilosi, Marco; Facchetti, Fabio; Caliò, Anna; Zamò, Alberto; Brunelli, Matteo; Martignoni, Guido; Rossi, Andrea; Montagna, Licia; Piccoli, Paola; Dubini, Alessandra; Tironi, Andrea; Tomassetti, Sara; Poletti, Venerino; Doglioni, Claudio
• Is Part Of: Leukemia & lymphoma. Volume 55:Issue 11(2014:Nov.)
• Page Start: 2620
• Page End: 2626
• Publication Date: 2014-11
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2014.887713
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>The clonal/neoplastic nature of Langerhans cell histiocytosis (LCH) has recently been demonstrated by a high prevalence of <italic>BRAF</italic> mutations, including pulmonary LCH (PLCH). We hypothesized that <italic>BRAF</italic>-induced senescence, as demonstrated in nevi and melanoma, is involved in the pathogenesis of LCH and PLCH. In a series of pulmonary (19 cases) and non-pulmonary LCH (19 cases), including five aggressive cases, we investigated occurrence of the <italic>BRAF</italic> V600E mutation by molecular analysis and/or immunohistochemistry using a validated antibody (VE1). The expression of cell-senescence markers p16^INK4a and p21^CIP1/WAF1 was also immunohistochemically investigated. We demonstrated that 6/19 cases of LCH and 12/19 cases of PLCH were VE1 positive, matching with molecular analysis, and in all cases both p16^INK4a and p21^CIP1/WAF1 were expressed, irrespective of <italic>BRAF</italic> mutation status. Interestingly, all the aggressive cases did not express p16^INK4a, thus suggesting that loss of senescence control could be related to clinical aggressiveness of LCH, as in melanoma.</p> </abstract>