ArticleJournal of cancer research and clinical oncology2012
High KIT and PDGFRA are associated with shorter patients survival in gastroenteropancreatic neuroendocrine tumors, but mutations are a rare event.
Article in Journal of cancer research and clinical oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Nuclear survivin is a prognosticator in gastroenteropancreatic neuroendocrine neoplasms: a meta-analysis.Journal of cancer research and clinical oncology · 2022Pooled it
- Everything you ever wanted to know about cancer stem cells in neuroendocrine neoplasms but were afraid to ask.Endocrine oncology (Bristol, England) · 2024Review
- Article
- Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases.International journal of molecular sciences · 2020Article
- Exploration of the relationships between tumor mutation burden with immune infiltrates in clear cell renal cell carcinoma.Annals of translational medicine · 2019Article
- PDGFRα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors.Cancer biology & therapy · 2019Article
- [Neuroendocrine neoplasia of the stomach : What is new?]Der Pathologe · 2017Article
- Genes involved in angiogenesis and mTOR pathways are frequently mutated in Asian patients with pancreatic neuroendocrine tumors.International journal of biological sciences · 2016Article
- Article
- Neuroendocrine Carcinomas of the Gastroenteropancreatic System: A Comprehensive Review.Diagnostics (Basel, Switzerland) · 2015Review
- Platelet-derived growth factors induced lymphangiogenesis: evidence, unanswered questions and upcoming challenges.Archives of medical science : AMS · 2015Article
- The search for the primary tumor in metastasized gastroenteropancreatic neuroendocrine neoplasm.Clinical & experimental metastasis · 2014Article
- Pulmonary well-differentiated fetal adenocarcinoma with platelet-derived growth factor receptor (PDGFR)α expression.Cancer biology & therapy · 2012Article
- Safety and efficacy of sunitinib in patients with unresectable pancreatic neuroendocrine tumors.Clinical Medicine Insights. Oncology · 2012Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purpose(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 expression.
methodsGastroenteropancreatic 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 expression.
resultsHigh 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 disease-specific survival (P = 0.003, P = 0.018, respectively). In multivariate analysis expression of PDGFRA, radicality of surgical treatment and WHO grading influenced disease-specific 10-year survival independently (P = 0.032, P = 0.001 and P = 0.008, respectively). Mutational analysis of highly expressed specimens (n = 51) reveals a novel mutation of KIT in exon 11 (K558N_V559insP) in a well-differentiated metastatic pancreatic neuroendocrine tumor.
conclusionsHigh 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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