Targeting c-KIT, PDGFR in cancer of unknown primary: a screening study for molecular markers of benefit

被引:12
作者
Dova, L. [2 ]
Pentheroudakis, G. [1 ]
Golfinopoulos, V. [1 ]
Malamou-Mitsi, V. [3 ]
Georgiou, I. [4 ]
Vartholomatos, G. [2 ]
Ntemou, A. [5 ]
Fountzilas, G. [6 ]
Pavlidis, N. [1 ]
机构
[1] Ioannina Univ Hosp, Dept Med Oncol, Ioannina 45110, Greece
[2] Ioannina Univ Hosp, Mol Biol Unit, Hematol Lab, Ioannina 45110, Greece
[3] Ioannina Univ Hosp, Dept Pathol, Ioannina 45110, Greece
[4] Ioannina Univ Hosp, Dept Obstet & Gynaecol, Genet Unit, Ioannina 45110, Greece
[5] Chatzikosta Gen Hosp, Dept Pathol, Ioannina, Greece
[6] Aristotle Univ Thessaloniki, Sch Med, Papageorgiou Gen Hosp, Dept Med Oncol, Macedonia, Greece
关键词
C-KIT; PDGFR; mutations; immunohistochemistry; cancer of unknown primary;
D O I
10.1007/s00432-007-0341-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:697 / 704
页数:8
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