Immunohistochemical and Molecular Cytogenetic Evaluation of Potential Targets for Tyrosine Kinase Inhibitors in Langerhans Cell Histiocytosis
GC Caponetti, RC Streblow, PA Althof, WG Sanger, TC Greiner, DD Weisenburger. University of Nebraska Medical Center, Omaha, NE
Background: Langerhans cell histiocytosis (LCH) is a rare disorder of the dendritic cell system with an unknown pathogenesis. Conventional therapy for LCH is usually effective but some cases are refractory or develop secondary toxicity. Thus, there is a need for innovative therapies. Recently, a case of LCH, that was refractory to conventional therapy, was reported to be PDGFRbeta+ by immunohistochemistry (IHC), while another case was found to be KIT+ by IHC. Both cases responded to imatinib mesylate (IM). In addition, FIP1L1-PDGFRalpha and ETV6-PDGFRbeta fusion gene-associated myeloid/lymphoid disorders have been shown to respond to IM. The aim of this study was to evaluate immunohistochemical and molecular markers in LCH that could identify cases amenable to be treated with tyrosine kinase inhibitors such as IM.
Design: We investigated 14 formalin-fixed, paraffin-embedded (FFPE) archival cases of LCH. Controls (n=12) included cases of inflammatory dermatitis (n=5) and dermatopathic lymphadenitis (n=7). We performed IHC using antibodies for s100, CD1a, KIT and PDGFRalpha. Fluorescence in situ hybridization (FISH) analysis using probes to the CHIC2 gene and the ETV6-PDGFRbeta fusion gene was performed on FFPE sections.
Results: In 13 (92%) cases of LCH, Langerhans cells (LCs) were focally and weakly to moderately positive for PDGFRalpha by IHC, as were 9 control cases. Also, some histiocytes were weakly positive. All cases were negative for KIT. FISH studies performed on cases with adequate DNA were negative in 8 cases of LCH and in 7 control cases.
Conclusions: Our findings demonstrate that the LCs in cases of LCH show focal and variable expression of PDGFRalpha by IHC, and this expression was also noted in other conditions. However, LCs in LCH and other cases did not express KIT. To our knowledge, this is the first study to show that the PDGFR genes are not rearranged in LCH. Our findings indicate that other immunohistochemical markers, such as PDGFRbeta, should also be investigated in LCH.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 218, Tuesday Morning