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Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis.
- Source :
- Leukemia & Lymphoma; Nov2014, Vol. 55 Issue 11, p2620-2626, 7p
- Publication Year :
- 2014
-
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<superscript>INK4a</superscript> and p21<superscript>CIP1/WAF1</superscript> 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<superscript>INK4a</superscript> and p21<superscript>CIP1/WAF1</superscript> were expressed, irrespective of BRAF mutation status. Interestingly, all the aggressive cases did not express p16<superscript>INK4a</superscript>, thus suggesting that loss of senescence control could be related to clinical aggressiveness of LCH, as in melanoma. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10428194
- Volume :
- 55
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Leukemia & Lymphoma
- Publication Type :
- Academic Journal
- Accession number :
- 98999553
- Full Text :
- https://doi.org/10.3109/10428194.2014.887713