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Targeting c-KIT, PDGFR in cancer of unknown primary: a screening study for molecular markers of benefit
L Dova1, G Pentheroudakis, V Golfinopoulos
1Hematological Laboratory, Molecular Biology Unit, Ioannina University Hospital, Ioannina, Greece.
Aims:
In view of available targeted therapies, we investigated the presence of c-kit, PDGFR gene mutations and protein expression in cancer of unknown primary (CUP) in order to study their contribution in pathogenesis, their prognostic value and potential as therapeutic targets.
Methods:
Mutations in hot spots c-kit exon 11 and PDGFR exons 12 and 18 were studied in paraffin-embedded tumour samples from 50 patients with CUP by means of PCR-based single-strand conformational polymorphism and protein expression by means of streptavidin-biotin immunoperoxidase assays. Molecular markers were screened for possible correlations with patient outcome.
Results:
No shifted band was detected in any of the polyacrylamide gel electrophoreses, indicating absence of c-kit exon 11 and PDGFR exon 12, 18 mutations. Immunohistochemical analysis in 37 tumours revealed positive membranous CD117 expression in 30 samples (81%) of which five exhibited strong (+3), four moderate (+2) and 21 weak (+1) staining. PDGFRa protein staining was seen in 15 out of 30 (50%) cases, mostly weak (13) and rarely moderate (1) or strong (1). The expression of KIT or PDGFRa protein did not correlate with the clinical outcome of the patients in our cohort.
Conclusions:
In a moderate-sized CUP patient cohort, KIT or PDGFRa protein overexpression is rare, does not have gross prognostic significance for survival and is not associated with presence of activating mutations.
Insights
KIT and PDGFRa gene mutations are absent in cancer of unknown primary (CUP). While KIT and PDGFRa protein expression is present, it does not correlate with patient survival or activating mutations in CUP.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cancer of Unknown Primary (CUP) presents a diagnostic challenge.
- Targeted therapies offer potential treatment avenues for specific cancer types.
Purpose of the Study:
- Investigate c-kit and PDGFR gene mutations and protein expression in CUP.
- Assess their role in pathogenesis, prognostic value, and therapeutic potential.
Main Methods:
- Analyzed 50 CUP tumor samples for c-kit exon 11 and PDGFR exons 12/18 mutations using PCR-SSCP.
- Assessed KIT and PDGFRa protein expression via immunohistochemistry.
- Correlated molecular markers with patient outcomes.
Main Results:
- No c-kit or PDGFR gene mutations were detected.
- KIT protein (CD117) expression was observed in 81% of tumors, predominantly weak.
- PDGFRa protein expression was found in 50% of tumors, mostly weak.
Conclusions:
- KIT or PDGFRa protein overexpression is rare in CUP.
- Protein expression did not show significant prognostic value for survival.
- Activating mutations in these genes are not associated with protein expression in CUP.
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