Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis

Marco Chilosi, Fabio Facchetti, Anna Caliò, Alberto Zamò, Matteo Brunelli, Guido Martignoni, Andrea Rossi, Licia Montagna, Paola Piccoli, Alessandra Dubini, Andrea Tironi, Sara Tomassetti, Venerino Poletti, Claudio Doglioni

Research output: Contribution to journalArticlepeer-review

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 p16INK4a and p21CIP1/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 p16INK4a and p21CIP1/WAF1 were expressed, irrespective of BRAF mutation status. Interestingly, all the aggressive cases did not express p16INK4a, thus suggesting that loss of senescence control could be related to clinical aggressiveness of LCH, as in melanoma.

Original languageEnglish
Pages (from-to)2620-2626
Number of pages7
JournalLeukemia and Lymphoma
Volume55
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

Keywords

  • BRAF mutation
  • P16<sup>INK4a</sup>
  • P21<sup>CIP1/WAF1</sup>
  • PLCH
  • Senescence in LCH

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Medicine(all)

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