Page 33 - SDIR5 Abstract book 21 12 2021.

RADIOBIOLOGY

Potential predictive role of K-ras gene mutation and BCL2 protein expression status in locally
advanced rectal cancers treated with neoadjuvant chemoradiotherapy

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Bojana Kožik , Milena Krajnović , Snežana Jovanović Ćupić , Nikola Kokanov , Ana Božović , Lidija
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Todorović , Vesna Mandušić
1 Laboratory for Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences,
National Institute of Republic of Serbia, University of Belgrade, Serbia

Background: Rectal cancer represents approximately 30% of cases of colorectal carcinoma and locally
advanced stages of rectal cancers (LARC) remain a great clinical challenge due to chemoresistance and high
local recurrence rate. The current management of LARC involves neoadjuvant chemoradiotherapy
(neoCRT) before surgery. Since only a subset of patients benefit from this preoperative treatment, the
development of reliable molecular biomarkers is required. In this retrospective study, we investigated the
mutation status of K-ras proto-oncogene, as well as the expression level of apoptosis regulator protein,
BCL2, to evaluate their potential predictive role in LARC. Patients and Methods: K-ras gene mutation status
was determined by direct sequencing, while BCL2 protein expression was detected immunohistochemically
(semi-quantitatively method) in pre-therapeutic and pre-operative biopsy specimens of 61 patients with
LARC treated with neoCRT. Results: According to the results of this study, K-ras mutation status and BCL2
expression status were mutually independent events. In general, K-ras mutation status did not affect the
response to CRT, while in the group of patients with high BCL2 expression was observed a tendency toward
a worse response to the same treatment (p=0.098). However, the subgroup of patients with the
simultaneous presence of K-ras mutation and high BCL2 expression showed significantly worse response to
neoCRT (p=0.022). Conclusion: Obtained results strongly suggest that combined analyses of molecular
aberrations in K-ras proto-oncogene and BCL2 anti-apoptotic protein expression level could have a
potential predictive role and important clinical relevance in the identification of LARC patient subgroups,
with a distinct pattern of response to neoCRT.
Keywords: BCL2 proteins, K-ras gene, Neoadjuvant Chemoradiotherapy, Predictive Medicine, Rectal
Cancer.

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