Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics
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2016
Authors
Krajnović, Milena M.Marković, Bojana
Knežević-Ušaj, Slavica
Nikolic, Ivan
Stanojevic, Maja
Nikolić, Valentina
Siljic, Marina
Jovanović-Ćupić, Snežana P.
Dimitrijević, Bogomir B.
Article (Published version)
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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.
Keywords:
Rectal cancer / KRAS / VEGF / Biomarkers / PrognosisSource:
Pathology Research and Practice, 2016, 212, 7, 598-603Funding / projects:
- Molecular determinants for tumor marker design (RS-MESTD-Basic Research (BR or ON)-173049)
- Phylogenetic anaysis and molecular evolution of highly variable viruses: coinfections, host-pathogene interactions (RS-MESTD-Basic Research (BR or ON)-175024)
DOI: 10.1016/j.prp.2016.02.018
ISSN: 0344-0338
PubMed: 27184911
WoS: 000379274300002
Scopus: 2-s2.0-84966708513
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VinčaTY - JOUR AU - Krajnović, Milena M. AU - Marković, Bojana AU - Knežević-Ušaj, Slavica AU - Nikolic, Ivan AU - Stanojevic, Maja AU - Nikolić, Valentina AU - Siljic, Marina AU - Jovanović-Ćupić, Snežana P. AU - Dimitrijević, Bogomir B. PY - 2016 UR - https://vinar.vin.bg.ac.rs/handle/123456789/1164 AB - 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. T2 - Pathology Research and Practice T1 - Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics VL - 212 IS - 7 SP - 598 EP - 603 DO - 10.1016/j.prp.2016.02.018 ER -
@article{ author = "Krajnović, Milena M. and Marković, Bojana and Knežević-Ušaj, Slavica and Nikolic, Ivan and Stanojevic, Maja and Nikolić, Valentina and Siljic, Marina and Jovanović-Ćupić, Snežana P. and Dimitrijević, Bogomir B.", year = "2016", abstract = "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.", journal = "Pathology Research and Practice", title = "Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics", volume = "212", number = "7", pages = "598-603", doi = "10.1016/j.prp.2016.02.018" }
Krajnović, M. M., Marković, B., Knežević-Ušaj, S., Nikolic, I., Stanojevic, M., Nikolić, V., Siljic, M., Jovanović-Ćupić, S. P.,& Dimitrijević, B. B.. (2016). Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics. in Pathology Research and Practice, 212(7), 598-603. https://doi.org/10.1016/j.prp.2016.02.018
Krajnović MM, Marković B, Knežević-Ušaj S, Nikolic I, Stanojevic M, Nikolić V, Siljic M, Jovanović-Ćupić SP, Dimitrijević BB. Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics. in Pathology Research and Practice. 2016;212(7):598-603. doi:10.1016/j.prp.2016.02.018 .
Krajnović, Milena M., Marković, Bojana, Knežević-Ušaj, Slavica, Nikolic, Ivan, Stanojevic, Maja, Nikolić, Valentina, Siljic, Marina, Jovanović-Ćupić, Snežana P., Dimitrijević, Bogomir B., "Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics" in Pathology Research and Practice, 212, no. 7 (2016):598-603, https://doi.org/10.1016/j.prp.2016.02.018 . .