Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics
| Autor: | Bogomir Dimitrijević, Snežana Jovanović Ćupić, Milena Krajnović, Maja Stanojevic, Bojana M. Marković, Ivan Nikolic, Slavica Knežević-Ušaj, Marina Siljic, Valentina Nikolić |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine Oncology medicine.medical_specialty Colorectal cancer DNA Mutational Analysis Disease Biology medicine.disease_cause Pathology and Forensic Medicine Proto-Oncogene Proteins p21(ras) 03 medical and health sciences chemistry.chemical_compound Exon 0302 clinical medicine Internal medicine medicine KRAS Humans Neoplasm Invasiveness Rectal cancer Gene Aged Aged 80 and over Rectal Neoplasms Cell Biology Middle Aged medicine.disease Prognosis VEGF digestive system diseases 3. Good health Survival Rate Vascular endothelial growth factor 030104 developmental biology chemistry 030220 oncology & carcinogenesis Mutation (genetic algorithm) Cancer research Female Kras mutation Biomarkers |
| Zdroj: | Pathology Research and Practice |
| Popis: | In this study, we investigated the mutation status of KRAS gene in pretherapeutic and preoperative biopsies in 63 specimens of locally advanced rectal cancers in order to evaluate its potential predictive and/or prognostic role. Regions of interest of KRAS exon 2 were amplified and visualized on 2% agarose gel. Obtained PCR products were subjected to direct sequencing. KRAS mutations were detected in 35% of patients, 91% of which were located in codon 12 and 9% in codon 13. In general, KRAS mutation status did not affect the response to neoadjuvant chemoradiotherapy (CRT). However, patients harboring mutated KRAS gene, simultaneously with high vascular endothelial growth factor (VEGF) expression, exhibited a worse response to CRT (p = 0.030), a more frequent appearance of local recurrences and distant metastasis (p = 0.003), and shorter overall survival (p = 0.001) compared to all others. On the contrary, patients with GGT GT GCT KRAS mutation exhibited a significantly better response to CRT than those with any other type of KRAS mutation (p = 0.017). Moreover, the presence of GGT GT GCT mutation was associated with low VEGF and Ki67 expression (p = 0.012 in both cases), parameters related to less aggressiveness of the disease. Our results suggest that KRAS mutation status could have some predictive and prognostic importance in rectal cancer when analyzed together with other parameters, such as VEGF and Ki67 expression. In addition, it seems that not only the presence but the type of KRAS mutation is important for examining its impact on CRT response. (C) 2016 Elsevier GmbH. All rights reserved. |
| Databáze: | OpenAIRE |
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