Expression of KIT and PDGFR is associated with a good prognosis in neuroblastoma

Akira Shimada, Junko Hirato, Minoru Kuroiwa, Akira Kikuchi, Ryoji Hanada, Kimiko Wakai, Yasuhide Hayashi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)213-217
Number of pages5
JournalPediatric Blood and Cancer
Volume50
Issue number2
DOIs
Publication statusPublished - Feb 2008
Externally publishedYes

Fingerprint

Neuroblastoma
Receptor Protein-Tyrosine Kinases
Messenger RNA
Tumor Cell Line
Mutation
Paraffin
Cell Movement
Disease Progression
Neoplasms
Protein Isoforms
Phosphotransferases
Immunohistochemistry
Neoplasm Metastasis
Cell Line
Polymerase Chain Reaction
Growth
Proteins

Keywords

  • FLT3
  • KIT
  • Neuroblastoma
  • PDGFR
  • Receptor tyrosine kinase

ASJC Scopus subject areas

  • Cancer Research
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Shimada, A., Hirato, J., Kuroiwa, M., Kikuchi, A., Hanada, R., Wakai, K., & Hayashi, Y. (2008). Expression of KIT and PDGFR is associated with a good prognosis in neuroblastoma. Pediatric Blood and Cancer, 50(2), 213-217. https://doi.org/10.1002/pbc.21288

Expression of KIT and PDGFR is associated with a good prognosis in neuroblastoma. / Shimada, Akira; Hirato, Junko; Kuroiwa, Minoru; Kikuchi, Akira; Hanada, Ryoji; Wakai, Kimiko; Hayashi, Yasuhide.

In: Pediatric Blood and Cancer, Vol. 50, No. 2, 02.2008, p. 213-217.

Research output: Contribution to journalArticle

Shimada, A, Hirato, J, Kuroiwa, M, Kikuchi, A, Hanada, R, Wakai, K & Hayashi, Y 2008, 'Expression of KIT and PDGFR is associated with a good prognosis in neuroblastoma', Pediatric Blood and Cancer, vol. 50, no. 2, pp. 213-217. https://doi.org/10.1002/pbc.21288
Shimada, Akira ; Hirato, Junko ; Kuroiwa, Minoru ; Kikuchi, Akira ; Hanada, Ryoji ; Wakai, Kimiko ; Hayashi, Yasuhide. / Expression of KIT and PDGFR is associated with a good prognosis in neuroblastoma. In: Pediatric Blood and Cancer. 2008 ; Vol. 50, No. 2. pp. 213-217.
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abstract = "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.",
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AU - Shimada, Akira

AU - Hirato, Junko

AU - Kuroiwa, Minoru

AU - Kikuchi, Akira

AU - Hanada, Ryoji

AU - Wakai, Kimiko

AU - Hayashi, Yasuhide

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N2 - 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.

AB - 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.

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