Co-existence of BRAF V600E gene mutation in tumor and non-Tumoral surrounding tissues in colorectal cancer
OZTüRK, T. | Toptaş-Hekimo?lu, B. | Eronat, A.P. | Saygili, N. | Da?lar-Aday, A. | BAŞSüLLü, N. | İşbir, Turgay
Article | 2015 | In Vivo29 ( 5 ) , pp.577 - 584
Background/Aim: The murine sarcoma viral (VRaf) oncogene homolog B (BRAF) V600E mutation, which increases protein kinase activity in BRAF- mitogen-Activated protein kinase kinase (MEK) - extracellular signal-regulated kinases (ERK) (mitogen-Activated protein kinase (MAPK)) signaling, is found in 5-40% of all colorectal carcinoma cases. Proteins with this mutation are reported to be 130-fold more active, which results in induced proliferation, differentiation, cellular survival, and angiogenesis. The aim of the present study was to investigate tumor tissues, together with the surrounding non-Tumoral tissues, for BRAF mutation presenc . . .e, which may be an indicator for possible recurrence or prognosis as in the 'field carcinogenesis' model. Materials and Methods: The BRAF V600E genotype of 152 colorectal adenocarcinoma paraffin-embedded specimens were determined by mutant-Allele-specific amplification-polymerase chain reaction. Results: According to our results, the presence of BRAF mutation increases risk of lymph node invasion by 1.55-fold [X2=3.83, p=0.05, odds ratio (OR)=1.55, 95% confidence interval (CI)=1.00-2.42], histologically medium or high-grade tumor by 1.60-fold (X2=4.34, p=0.030, OR=1.60, 95% CI=1.03-2.48), vascular invasion by 1.55-fold (X2=3.55, p=0.05, OR=1.55, 95% CI=0.99-2.42), perineural invasion by 1.50-fold (X2=3.16, p=0.07, OR=1.5, 95% CI=0.96-2.33) and the combination of these poor prognostic features by 1.54-fold (X2=2.47, p=0.11, OR=1.54, 95% CI=0.93-2.53). We also found that females are more prone to having the mutation and that being female increases the risk of having this mutation by 1.54-fold (X2=3.58, p=0.05, OR=1.54, 95% CI=0.97-2.44). Conclusion: BRAF V600E mutation in non-Tumoral surrounding tissue in patients with colorectal cancer may be used as a valuable marker to foresee clinical outcome or a possible recurrence. To our knowledge, this was the first study to take into consideration the non-Tumoral surrounding tissues in addition to the tumor tissue
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