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KIT, PDGFRα and EGFR analysis in nephroblastoma

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Abstract

Nephroblastoma prognosis has dramatically improved, but an unfavourable prognostic subgroup warrants development of novel therapeutic strategies. Selective KIT, PDGFRα and epidermal growth factor receptor (EGFR) tyrosine kinase inhibition evolved as powerful targeted therapy for gastrointestinal stromal tumours and non-small-cell lung cancer. To investigate a potential role for tyrosine kinase inhibition, we analyzed 209 nephroblastomas for immunohistochemical KIT and EGFR expression, 63 nephroblastomas for mutations in KIT exons 9, 11, 13, EGFR exons 18, 19, 20 and 21, and all 209 nephroblastomas for PDGFRα exons 12, 14 and 18. Twenty-two tumours (10.5%) expressed KIT, 31 (14.8%) EGFR, and 10 (4.8%) both KIT and EGFR, respectively. KIT expression was relatively more common among high-risk tumours (6/27; 22.3%) compared to low-/intermediate-risk tumours (26/181; 14.4%). Nine patients deceased, four of which had high-risk tumours with KIT expression in two of four and EGFR expression in one of four. There were no KIT, PDGFRα or EGFR mutations. Our results suggest no significant contribution of KIT, EGFR or PDGFRα mutations to nephroblastoma pathogenesis. Despite a trend towards association of immunohistochemical KIT and EGFR expression with poor outcome in high-risk nephroblastomas, statistical analysis did not yield significant correlations in this subgroup. Therefore, it remains open if KIT, PDGFRα or EGFR tyrosine kinase inhibition constitute a therapeutic target in nephroblastoma in the absence of KIT, PDGFRα or EGFR mutations.

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Acknowledgments

We are grateful to Barbara Stalder, Molecular Pathology Section, Institute for Pathology, University Hospital Basel, Switzerland for excellent performance of immunohistochemistry and to Melanie Schlangstedt, Institute for Clinical Chemistry and Laboratory Medicine at the University of Regensburg, Regensburg, Germany for PDGFRα sequence analysis. The study experiments comply with the current laws in the country in which they were performed.

This study was funded by a grant of the Basel Cancer League to EB.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Institute for Pathology, Basel University Hospital, Schoenbeinstrasse 40, CH-4031, Basel, Switzerland

    Sylvia C. Wetli, Alex Rufle, Anja Foerster, Michel Bihl, Luigi Tornillo, Michael J. Mihatsch, Inti Zlobec & Elisabeth Bruder

  2. Institute for Pathology, University Hospital Schleswig-Holstein Campus Kiel, Michaelisstrasse 11, 24105, Kiel, Germany

    Ivo Leuschner & Dieter Harms

  3. Department of Paediatric Oncology, University Children’s Hospital, Building 9, 66421, Homburg, Germany

    Norbert Graf & Roikos Furtwaengler

  4. Department of Paediatric Oncology/Haematology, University Children’s Hospital, Römergasse 8, CH-4005, Basel, Switzerland

    Michael Paulussen

  5. Institute for Histologic and Cytologic Diagnostics, Dammweg 1, CH-5001, Aarau, Switzerland

    Jakob Briner

  6. Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef Strauß Allee 11, 93053, Regensburg, Germany

    Charalampos Aslanidis & Gerd Schmitz

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  1. Sylvia C. Wetli
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Correspondence to Elisabeth Bruder.

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Loc recur local recurrence, Meta metastasis, DOD death of disease, KIT % percent of tumour cells with immunohistochemical KIT expression per positive punch cylinder, EGFR % percent of tumour cells with immunohistochemical EGFR expression per positive punch cylinder, Pre-op Chemo preoperative chemotherapy, Follow-up follow-up period indicated in months (XLS 56.5 kb)

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Wetli, S.C., Leuschner, I., Harms, D. et al. KIT, PDGFRα and EGFR analysis in nephroblastoma. Virchows Arch 452, 637–650 (2008). https://doi.org/10.1007/s00428-008-0605-x

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  • DOI: https://doi.org/10.1007/s00428-008-0605-x

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