TY - JOUR
T1 - BRAF V600E expression in langerhans cell histiocytosis
T2 - Clinical and immunohistochemical study on 25 pulmonary and 54 extrapulmonary cases
AU - Roden, Anja C.
AU - Hu, Xiaowen
AU - Kip, Sertac
AU - Parrilla Castellar, Edgardo R.
AU - Rumilla, Kandelaria M.
AU - Vrana, Julie A.
AU - Vassallo, Robert
AU - Ryu, Jay H.
AU - Yi, Eunhee S.
PY - 2014/4
Y1 - 2014/4
N2 - Pulmonary Langerhans cell histiocytosis (PLCH) has been postulated to be a smoking-related non-neoplastic condition, distinct from extrapulmonary LCH, which is generally regarded as a clonal, neoplastic process. Recent genomic studies demonstrated BRAF V600E mutation in 38% to 57% of extrapulmonary LCH cases by polymerase chain reaction. We evaluated the BRAF V600E expression by immunohistochemistry (IHC) in PLCH and extrapulmonary LCH cases. We compared BRAF V600E expression in PLCH and extrapulmonary LCH with BRAF V600E mutation status. Our study included 25 PLCH (age 42.0±11.4, 10 men) and 54 extrapulmonary LCH (age 27.6±21.8, 37 men) cases. Seven of 25 (28%) PLCH cases were positive for BRAF V600E expression (age 45.3±8.1, 2 men); 6 of 7 cases with BRAF V600E expression were also positive by mutation analysis. Nineteen of 54 (35%) extrapulmonary LCH cases were positive for BRAF V600E expression (age 27.6±22.1, 13 men) as well as mutation. Two IHC-negative cases, however, were positive by mutation analysis. All PLCH cases were current or former smokers, whereas 28 of 54 extrapulmonary LCH patients were never-smokers. The cumulative tobacco exposure at the time of diagnosis was significantly higher in BRAF V600E-positive than in BRAF V600E-negative PLCH patients (mean pack-years 48.3 vs. 23.7, 2-tailed t test P=0.01). BRAF V600E expression by IHC correlated with BRAF V600E mutational status in most of the cases in our study except in 3 patients (4.4%). In conclusion, a subset of PLCH with BRAF V600E expression may be a clonal proliferative process, in which cigarette smoking might play a role.
AB - Pulmonary Langerhans cell histiocytosis (PLCH) has been postulated to be a smoking-related non-neoplastic condition, distinct from extrapulmonary LCH, which is generally regarded as a clonal, neoplastic process. Recent genomic studies demonstrated BRAF V600E mutation in 38% to 57% of extrapulmonary LCH cases by polymerase chain reaction. We evaluated the BRAF V600E expression by immunohistochemistry (IHC) in PLCH and extrapulmonary LCH cases. We compared BRAF V600E expression in PLCH and extrapulmonary LCH with BRAF V600E mutation status. Our study included 25 PLCH (age 42.0±11.4, 10 men) and 54 extrapulmonary LCH (age 27.6±21.8, 37 men) cases. Seven of 25 (28%) PLCH cases were positive for BRAF V600E expression (age 45.3±8.1, 2 men); 6 of 7 cases with BRAF V600E expression were also positive by mutation analysis. Nineteen of 54 (35%) extrapulmonary LCH cases were positive for BRAF V600E expression (age 27.6±22.1, 13 men) as well as mutation. Two IHC-negative cases, however, were positive by mutation analysis. All PLCH cases were current or former smokers, whereas 28 of 54 extrapulmonary LCH patients were never-smokers. The cumulative tobacco exposure at the time of diagnosis was significantly higher in BRAF V600E-positive than in BRAF V600E-negative PLCH patients (mean pack-years 48.3 vs. 23.7, 2-tailed t test P=0.01). BRAF V600E expression by IHC correlated with BRAF V600E mutational status in most of the cases in our study except in 3 patients (4.4%). In conclusion, a subset of PLCH with BRAF V600E expression may be a clonal proliferative process, in which cigarette smoking might play a role.
KW - BRAF V600E
KW - Clonal
KW - Langerhans cell histiocytosis
KW - Pulmonary
KW - Smoking
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U2 - 10.1097/PAS.0000000000000129
DO - 10.1097/PAS.0000000000000129
M3 - Article
C2 - 24625419
AN - SCOPUS:84896634002
SN - 0147-5185
VL - 38
SP - 548
EP - 551
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 4
ER -