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: BRAF mutation -- senescence in LCH -- PLCH -- p21CIP1/WAF1 -- p16INK4a; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2014.887713
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: The clonal/neoplastic nature of Langerhans cell histiocytosis (LCH) has recently been demonstrated by a high prevalence of BRAF mutations, including pulmonary LCH (PLCH). We hypothesized that BRAF -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 BRAF 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 BRAF 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.