Immunohistochemical and molecular cytogenetic evaluation of potential targets for tyrosine kinase inhibitors in Langerhans cell histiocytosis

Gabriel C. Caponetti, Roberto N. Miranda, Pamela A. Althof, Renae C. Dobesh, Warren G. Sanger, L. Jeffrey Medeiros, Timothy Charles Greiner, Dennis D. Weisenburger

Research output: Contribution to journalArticle

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Abstract

Langerhans cell histiocytosis is a rare disorder of Langerhans cells, a component of the dendritic cell system, with an unknown pathogenesis. Conventional therapy for patients with Langerhans cell histiocytosis is usually effective, but some patients are refractory to treatment or develop toxicity. Thus, there is a need for innovative therapies. Recently, some cases of Langerhans cell histiocytosis were reported to express platelet-derived growth factor receptors α and β or c-KIT by immunohistochemistry, and some of these patients had a clinical response to imatinib mesylate. Other hematologic disorders with PDGFRα or PDGFRβ gene rearrangements also have responded to imatinib mesylate. The aim of this study was to evaluate immunohistochemical and molecular markers in Langerhans cell histiocytosis that would identify cases for possible treatment with tyrosine kinase inhibitors. We investigated formalin-fixed, paraffin-embedded tissue sections from 14 cases of Langerhans cell histiocytosis. As controls, we included cases of inflammatory dermatitis (n = 5) and dermatopathic lymphadenitis (n = 7). We performed immunohistochemistry for S100, CD1a, c-KIT, and platelet-derived growth factor receptors α and β. Fluorescence in situ hybridization analysis to detect rearrangements of the PDGFRα or PDGFRβ genes was also performed. Four (28.5%) of 14 cases of Langerhans cell histiocytosis were positive for platelet-derived growth factor receptor α, whereas absent/weak expression was seen in 10 cases and all controls. All cases were negative for platelet-derived growth factor receptor β and c-KIT. The fluorescence in situ hybridization studies were also negative in all 8 cases with adequate quality DNA. Our findings suggest that a subset of cases of Langerhans cell histiocytosis may be treated with tyrosine kinase inhibitors due to the expression of platelet-derived growth factor receptor α. Clinical trials that evaluate the use of tyrosine kinase inhibitors in Langerhans cell histiocytosis seem warranted and should evaluate these markers.

Original languageEnglish (US)
Pages (from-to)2223-2228
Number of pages6
JournalHuman Pathology
Volume43
Issue number12
DOIs
StatePublished - Dec 1 2012

Fingerprint

Langerhans Cell Histiocytosis
Cytogenetics
Protein-Tyrosine Kinases
Platelet-Derived Growth Factor Receptors
Fluorescence In Situ Hybridization
Immunohistochemistry
Lymphadenitis
Investigational Therapies
Langerhans Cells
Gene Rearrangement
Dermatitis
Cellular Structures
Paraffin
Dendritic Cells
Formaldehyde
Therapeutics
Clinical Trials
DNA

Keywords

  • Imatinib
  • Langerhans cell histiocytosis
  • Platelet-derived growth factor receptor
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Caponetti, G. C., Miranda, R. N., Althof, P. A., Dobesh, R. C., Sanger, W. G., Medeiros, L. J., ... Weisenburger, D. D. (2012). Immunohistochemical and molecular cytogenetic evaluation of potential targets for tyrosine kinase inhibitors in Langerhans cell histiocytosis. Human Pathology, 43(12), 2223-2228. https://doi.org/10.1016/j.humpath.2012.03.014

Immunohistochemical and molecular cytogenetic evaluation of potential targets for tyrosine kinase inhibitors in Langerhans cell histiocytosis. / Caponetti, Gabriel C.; Miranda, Roberto N.; Althof, Pamela A.; Dobesh, Renae C.; Sanger, Warren G.; Medeiros, L. Jeffrey; Greiner, Timothy Charles; Weisenburger, Dennis D.

In: Human Pathology, Vol. 43, No. 12, 01.12.2012, p. 2223-2228.

Research output: Contribution to journalArticle

Caponetti, Gabriel C. ; Miranda, Roberto N. ; Althof, Pamela A. ; Dobesh, Renae C. ; Sanger, Warren G. ; Medeiros, L. Jeffrey ; Greiner, Timothy Charles ; Weisenburger, Dennis D. / Immunohistochemical and molecular cytogenetic evaluation of potential targets for tyrosine kinase inhibitors in Langerhans cell histiocytosis. In: Human Pathology. 2012 ; Vol. 43, No. 12. pp. 2223-2228.
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