ИСТИНА

Background & Objectives: Adenocarcinomas account for at least 20% of all cervical cancers. This histological subtype represents a heterogeneous group of tumors that differ in the profile of molecular abnormalities and response to treatment. The targeted drug has been approved in a number of cancers as it has been shown to improve outcomes in patients with activating somatic mutations of KRAS gene. The aim of the present work is to investigate the frequency of these mutations among different histological variants of cervical adenocarcinoma, which may help in the search for personalized treatment strategies. Methods: Surgical specimens were collected from 24 patients with cervical adenocarcinoma. Distribution by histologic types was as follows: usual 50% (12/24), endometrioid 25% (6/24), mucinous, intestinal subtype 4,1% (1/24), mesonephral 8,3% (2/24), villoglandular 4,1% (1/24), serous-like 8,3% (2/24). DNA was isolated from a representative formalin-fixed, paraffin-embedded (FFPE) tumor tissue block by phenol-chloroform extraction using a DNA isolation kit (BioLink LLC, Russia). DNA samples were tested for mutations in codons G12X, G13X, Q61X and A146X of KRAS gene by real-time PCR using Real-time- PCR-KRAS-4R kit (BioLink LLC, Russia) according to the manufacturer's instructions. Reactions were performed on the CFX96 amplifier (Bio-Rad Laboratories, USA) according to the following protocol: 1 cycle - 95oC 3 min; 48 cycles - 95oC 15 sec, 55oC 40 sec. PCR products of KRAS gene with mutations were detected in 5'-exonuclease reaction using TaqMan probe labeled with fluorophore. Results: The frequency of KRAS gene mutations in cervical adenocarcinoma was 16,67% (4/24). All specimens with the identified mutation had endometrioid histologic variant and no mutations were found among other histologic variants. According to the results, KRAS gene mutations were more frequent in endometrioid histologic variant of cervical adenocarcinoma (p=0,0004). Conclusion: KRAS gene mutation may be considered as a potential therapeutic target in the endometrioid histologic variant of cervical adenocarcinoma.