Authors: Thomas Knösel Yuan Chen Annelore AltendorfHofmann Christine Danielczok Martin Freesmeyer Utz Settmacher Christine Wurst Stefan Schulz Lin Lin Yang Iver Petersen
Publish Date: 2011/12/08
Volume: 138, Issue: 3, Pages: 397-403
Abstract
1 To test whether in genomewide expression profiling differentially expressed genes were also distinct on the protein level including KIT and PDGFRA 2 to correlate the expression with clinicopathological parameters 3 to identify activating mutations that might be eligible for tyrosine kinase inhibitor therapy by mutational analysis of tumors with high expressionGastroenteropancreatic neuroendocrine tumors GEP NETs from 119 patients were analyzed for protein expression of ten biomarkers Mutational analysis of KIT exon 9 13 11 and 17 and PDGFRA exons 12 and 18 was performed on those samples that showed high protein expressionHigh KIT expression was observed in 13 of all specimens PDGFRA in 33 CK19 in 26 CK7 in 2 CK20 in 5 S100 in 6 CD56 in 25 Chromogranin in 55 and Synapthophysin in 80 High expression of KIT and PDGFRA was significantly correlated with shorter diseasespecific survival P = 0003 P = 0018 respectively In multivariate analysis expression of PDGFRA radicality of surgical treatment and WHO grading influenced diseasespecific 10year survival independently P = 0032 P = 0001 and P = 0008 respectively Mutational analysis of highly expressed specimens n = 51 reveals a novel mutation of KIT in exon 11 K558N V559insP in a welldifferentiated metastatic pancreatic neuroendocrine tumorHigh expression of KIT and PDGFRA was significantly correlated with shorter patients survival and could serve as prognostic marker Mutations of the KIT gene might open new avenues for tyrosine kinase inhibitor therapy in a subset of patients with advanced pancreatic neuroendocrine tumors
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