摘要
Abstract
Objective To investigate EGFR, PDGFRA and VEGFR2 RTKs overexpression and activating gene mu-tations in a cohort of 30 colon cancer patients sample. Methods EGFR, PDGFRA and VEGFR2 immunohistochem-istry was performed in all samples, followed by DNA isolation from the gross macroscopically dissection of the neo-plastic area. Screening for EGFR (exons18-21) and PDGFRA (exons12, 14 and 18) mutations was done by PCR-sin-gle-strand conformational polymorphism (PCR-SSCP). Results Despite the presence of EGFR immunohistochemical positive reactions in 43 % (13/30) of the samples, no EGFR activating mutations in the hotspot region (exons18-21) were identified. A silent base substitution (CAG > CAA) in EGFR exon 20 at codon 787 (Q787Q) was found in 17 cases (56 %). All PDGFRA immunohistochemical reactions were positive and consistently observed in the stromal component, staining fibroblasts and endothelial cells, as well as in the cytoplasm of malignant cells. No activating PDGFRA mutations were found, yet, several silent mutations were observed, such as a base substitution in exon 12 (CCA > CCG) at codon 567 (P567P) in 9 cases and in exon18 (GTC > GTT) at codon 824 (V824V) in 4 cases. We also observed the presence of base substitutions in intron 14 (IVS14 +3G >A and IVS14 +49G >A) in two differ-ent cases, and in intron 18 (IVS18-50 insA) in 4 cases. VEGFR2 positivity was observed in 22 of 30 cases (73.3%),and was significantly associated with lack of metastasis ( =0.038). Conclusions Despite the absence of EGFR and PDGFRA activating mutations, the presence of overexpression of these three important therapeutic targets in a subset of cases may be important in predicting the sensitivity of colon cancer to specific anti-RTKs drugs.关键词
表皮生长因子受体/血小板源性生长因子受体α多肽/血管内皮细胞生长因子受体2/结肠癌Key words
EGFR/PDGFRA/VEGFR2/colon cancer分类
医药卫生
