Expression of KIT and PDGFR is associated with a good prognosis in neuroblastoma
Akira Shimada MD
Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma, Japan
Search for more papers by this authorJunko Hirato MD
Department of Human Pathology, Gunma University Graduate School of Medicine, Gunma, Japan
Search for more papers by this authorMinoru Kuroiwa MD
Department of Pediatric Surgery, Gunma Children's Medical Center, Gunma, Japan
Search for more papers by this authorAkira Kikuchi MD
Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan
Search for more papers by this authorRyoji Hanada MD
Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan
Search for more papers by this authorKimiko Wakai CT
Department of Clinical laboratory, Gunma Children's Medical Center, Gunma, Japan
Search for more papers by this authorCorresponding Author
Yasuhide Hayashi MD
Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma, Japan
Gunma Children's Medical Center, 779, Shimohakoda, Hokkitsu, Shibukawa, Gunma 377-8577, Japan.===Search for more papers by this authorAkira Shimada MD
Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma, Japan
Search for more papers by this authorJunko Hirato MD
Department of Human Pathology, Gunma University Graduate School of Medicine, Gunma, Japan
Search for more papers by this authorMinoru Kuroiwa MD
Department of Pediatric Surgery, Gunma Children's Medical Center, Gunma, Japan
Search for more papers by this authorAkira Kikuchi MD
Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan
Search for more papers by this authorRyoji Hanada MD
Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan
Search for more papers by this authorKimiko Wakai CT
Department of Clinical laboratory, Gunma Children's Medical Center, Gunma, Japan
Search for more papers by this authorCorresponding Author
Yasuhide Hayashi MD
Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma, Japan
Gunma Children's Medical Center, 779, Shimohakoda, Hokkitsu, Shibukawa, Gunma 377-8577, Japan.===Search for more papers by this authorAbstract
Background
The clinical outcome of neuroblastoma (NB) depends on age, stage, and MYCN amplification. Receptor tyrosine kinases (RTKs) promote cell growth, migration, and metastasis in cancer cells, including NB. However, the correlation of the expression profile of RTKs with prognosis in NB remains controversial.
Procedure
Expression and mutation analysis of KIT, PDGFR, FLT3, RET, and TRKA mRNAs were performed in 24 NB cell lines and 40 tumor samples using RT-PCR followed by direct sequencing. Immunohistochemical analysis of KIT and PDGFR protein expression was also examined in 38 paraffin sections of NB tumor samples.
Results
The expression of KIT, PDGFRβ, and FLT3 mRNA was associated with NB in patients under 1 year (P < 0.02) and TRKA expression (P < 0.001). The loss of expression of these kinases was associated with MYCN amplification (P < 0.02) and advanced stages of disease in patients over 1 year of age (P < 0.005). PDGFRα mRNA expression was detected in all cell lines and tumor samples, and RET mRNA expression was not associated with any clinical parameters. Immunohistochemistry results showed the similar findings. We did not find any activating mutations in KIT, PDGFR, FLT3, or RET. Notably, the GNNK− isoform of KIT was predominant in all cell lines and clinical samples.
Conclusion
Expression of KIT, PDGFRβ, and FLT3 was associated with a good prognosis in NB. The loss of expression of these RTKs might correlate to the disease progression of NB. Pediatr Blood Cancer 2008;50:213–217. © 2007 Wiley-Liss, Inc.
Supporting Information
This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1545-5009/suppmat .
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| suppl_Table_II.doc36 KB | Supporting Information file suppl_Table_II.doc |
| Supplementary_Figure_1.doc62 KB | Supporting Information file Supplementary_Figure_1.doc |
| Supplementary_Figure_2.doc83.5 KB | Supporting Information file Supplementary_Figure_2.doc |
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