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 language | English |
|---|---|
| Pages (from-to) | 2620-2626 |
| Number of pages | 7 |
| Journal | Leukemia and Lymphoma |
| Volume | 55 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2014 |
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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)
Cite this
Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis. / 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.
In: Leukemia and Lymphoma, Vol. 55, No. 11, 01.11.2014, p. 2620-2626.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis
AU - Chilosi, Marco
AU - Facchetti, Fabio
AU - Caliò, Anna
AU - Zamò, Alberto
AU - Brunelli, Matteo
AU - Martignoni, Guido
AU - Rossi, Andrea
AU - Montagna, Licia
AU - Piccoli, Paola
AU - Dubini, Alessandra
AU - Tironi, Andrea
AU - Tomassetti, Sara
AU - Poletti, Venerino
AU - Doglioni, Claudio
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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.
AB - 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.
KW - BRAF mutation
KW - P16<sup>INK4a</sup>
KW - P21<sup>CIP1/WAF1</sup>
KW - PLCH
KW - Senescence in LCH
UR - http://www.scopus.com/inward/record.url?scp=84905657472&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905657472&partnerID=8YFLogxK
U2 - 10.3109/10428194.2014.887713
DO - 10.3109/10428194.2014.887713
M3 - Article
C2 - 24471909
AN - SCOPUS:84905657472
VL - 55
SP - 2620
EP - 2626
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
SN - 1042-8194
IS - 11
ER -