Platelet-Derived Growth Factor Receptor Beta (PDGFRb) Expression in Langerhans Cell Histiocytosis (LCH).

Abstract

On the basis of promising results obtained by imatinib mesilate in a patient with cerebral LCH with high expression of PDGFRb in the affected tissue (Case Report in press in the New Engl J Med), we evaluated PDGFRb expression by immunohistochemistry on banked LCH specimens.Methods: A 4 m m section obtained from formalin-fixed, paraffin-embedded specimens was incubated in a microwave oven for 15 min in 10 mmol/L buffered citrate pH 6.0, followed by immunohistochemical procedures to detect PDGFRb (using a rabbit polyclonal antibody, Santa Cruz Biotechnology Inc., CA) and KIT (CD117, Dako, Carpinteria, CA), diluted 1:50 and 1:300, respectively. A conventional avidin-biotin complex procedure was then applied, according to manufacturer's protocol. Briefly, the sections were washed and incubated with the primary antibody overnight at 4°C, then incubated with the secondary antibody. Positive staining was revealed by the DAB chromogen, followed by counterstaining with Mayer's hematoxilin. The slide was cover-slipped with a xilene-based mounting medium. The staining was scored as Neg, +1 (low expression), +2 (intermediate expression), or +3 (strong expression).Results. Up to now, we have analysed specimens from 9 patients (see Table). A strong PDGFRb expression with a predominant cytoplasmic localization was detected in 5 cases; two specimens had intermediate expression and two low expression. KIT expression was never observed. The study is ongoing, to evaluate a larger number of cases; however, in the limited series presented, 70% of cases had a significant PDGFRb expression. This finding may stimulate further clinical investigation on the use of tirosin kinase inhibitors in LCH.PDGFRß and KIT expression in LCH specimensCaseGender/AgeDisease siteKITPDGFRß1M/10ocular soft tissueNeg+1C2F/9skinNeg+3C/N3M/76skinNeg+2C4M/13boneNeg+3C5M/19boneNeg+3C6M/1boneNeg+1C7M/45oral mucosaNeg+3C8F/23brainNeg+2C9M/45oral mucosaNeg+3CC: cytoplasmic; N: nuclear