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Expression of KIT and PDGFR is associated with a good prognosis in neuroblastoma
Author(s) -
Shimada Akira,
Hirato Junko,
Kuroiwa Minoru,
Kikuchi Akira,
Hanada Ryoji,
Wakai Kimiko,
Hayashi Yasuhide
Publication year - 2008
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21288
Subject(s) - receptor tyrosine kinase , neuroblastoma , immunohistochemistry , medicine , cancer research , metastasis , tyrosine kinase , messenger rna , proto oncogene proteins c kit , platelet derived growth factor receptor , cancer , pathology , cell culture , receptor , biology , gene , stem cell factor , growth factor , stem cell , biochemistry , haematopoiesis , genetics
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.