title: Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics.
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>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>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.
authors.affiliation: University of Belgrade-Vinča Institute of Nuclear Sciences, 11001 Belgrade, Serbia. Electronic address: lena2mkd@yahoo.com.
authors.forename: Milena
authors.initials: M
authors.lastname: Krajnović
authors.affiliation: University of Belgrade-Vinča Institute of Nuclear Sciences, 11001 Belgrade, Serbia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Marković
authors.affiliation: Medical Faculty of Novi Sad, Oncology Institute of Vojvodina, 21204 Sremska Kamenica, Serbia.
authors.forename: Slavica
authors.initials: S
authors.lastname: Knežević-Ušaj
authors.affiliation: Medical Faculty of Novi Sad, Oncology Institute of Vojvodina, 21204 Sremska Kamenica, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Nikolić
authors.affiliation: University of Belgrade, Faculty of Medicine, Institute of Microbiology and Immunology, 11000 Belgrade, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Stanojević
authors.affiliation: University of Belgrade, Faculty of Medicine, Institute of Microbiology and Immunology, 11000 Belgrade, Serbia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Nikolić
authors.affiliation: University of Belgrade, Faculty of Medicine, Institute of Microbiology and Immunology, 11000 Belgrade, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Šiljić
authors.affiliation: University of Belgrade-Vinča Institute of Nuclear Sciences, 11001 Belgrade, Serbia.
authors.forename: Snežana
authors.initials: S
authors.lastname: Jovanović Ćupić
authors.affiliation: University of Belgrade-Vinča Institute of Nuclear Sciences, 11001 Belgrade, Serbia.
authors.forename: Bogomir
authors.initials: B
authors.lastname: Dimitrijević
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C117307:KRAS protein, human; D042461:Vascular Endothelial Growth Factor A; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Biomarkers; KRAS; Prognosis; Rectal cancer; VEGF