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


METHODS
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, PDGFRbeta, 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). PDGFRalpha 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.


CONCLUSIONS
Expression of KIT, PDGFRbeta, 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.
Shimada
Akira
A
Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma, Japan.
Hirato
Junko
J
Kuroiwa
Minoru
M
Kikuchi
Akira
A
Hanada
Ryoji
R
Wakai
Kimiko
K
Hayashi
Yasuhide
Y
D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D006801:Humans; D007223:Infant; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020917:Receptor, trkA / Q000096:biosynthesis / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051941:fms-Like Tyrosine Kinase 3 / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D020917:Receptor, trkA; D017479:Receptors, Platelet-Derived Growth Factor; D051941:fms-Like Tyrosine Kinase 3