Wetli, Sylvia C. and Leuschner, Ivo and Harms, Dieter and Rufle, Alex and Foerster, Anja and Bihl, Michel and Graf, Norbert and Furtwaengler, Roikos and Paulussen, Michael and Briner, Jakob and Aslanidis, Charalampos and Schmitz, Gerd and Tornillo, Luigi and Mihatsch, Michael J. and Zlobec, Inti and Bruder, Elisabeth (2008) KIT, PDGFR alpha and EGFR analysis in nephroblastoma. VIRCHOWS ARCHIV, 452 (6). pp. 637-650. ISSN 0945-6317,
Full text not available from this repository. (Request a copy)Abstract
Nephroblastoma prognosis has dramatically improved, but an unfavourable prognostic subgroup warrants development of novel therapeutic strategies. Selective KIT, PDGFR alpha 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 PDGFR alpha 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, PDGFR alpha or EGFR mutations. Our results suggest no significant contribution of KIT, EGFR or PDGFR alpha 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, PDGFR alpha or EGFR tyrosine kinase inhibition constitute a therapeutic target in nephroblastoma in the absence of KIT, PDGFR alpha or EGFR mutations.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GASTROINTESTINAL STROMAL TUMORS; GROWTH-FACTOR-RECEPTOR; NEOPLASTIC RENAL TISSUES; KINASE INHIBITOR STI571; OF-FUNCTION MUTATIONS; CELL LUNG-CANCER; WILMS-TUMOR; C-KIT; TYROSINE KINASE; SOLID TUMORS; nephroblastoma; KIT-PDGFR alpha-EGFR mutation analysis; tyrosine kinase inhibition; KIT-EGFR immunohistochemistry |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Nov 2020 09:21 |
| Last Modified: | 02 Nov 2020 09:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30876 |
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