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A. Mikhalenka



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    P1.02 - Poster Session with Presenters Present (ID 454)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-037 - Mutations of EGFR and KRAS Genes in Belorussian Patients Wich Non-Small Cell Lung Cancer (ID 5564)

      14:30 - 14:30  |  Author(s): A. Mikhalenka

      • Abstract

      Background:
      Mutations of the epidermal growth factor receptor (EGFR) cause increased activation of EGFR and sensitivity of patients with non-small cell lung cancer (NSCLC) to tyrosine kinase inhibitors (TKIs). The effectiveness of TKIs also depends on mutations of the KRAS gene that encodes small GTPase that is activated in response to a signal from EGFR and transmits it to the cascade of tyrosine kinases. Treatment of patients with KRAS mutations by TKIs is inefficient. Therefore, the research of these alterations plays an important role in determining the possibility of additional factors prognosis of NSCLC and adjusting individual tumor therapy. The aim of this study is to identify mutations in the exons 19 and 21 EGFR gene and in the exon 2 KRAS gene in patients with NSCLC.

      Methods:
      Analysis of mutations in the EGFR and KRAS genes was performed by PCR followed by sequencing DNA, which was extracted from the tumor and non-tumor lung tissues and blood samples of 97 patients with NSCLC (71 men, 26 women). 51 people have an adenocarcinoma (AC) and 46 people - squamous cell carcinoma (SCC).

      Results:
      Analysis of mutations in the EGFR gene showed that the frequency of classical mutations is 5,2% of deletions in exon 19 (p.E746_A750del and p.L747_P753>S) and 1,1% of p.L858R mutation in exon 21. All mutations were detected only in the tumor tissue of non-smoking women with AC. Thus, 27,3% of women with AK are carriers of mutations in EGFR gene. These types of mutations were not detected among men. Also in the researched group was identified silent mutation c.2508C>T in exon 21 in the tumor, non-tumor tissue and blood among 3,3% of patients. Analysis of mutations in exon 2 KRAS gene detected 3 types of mutations: p.G12D (1,03%), p.G12C (2,06%) и p.G13C (1,03%). The frequency of all mutations was 4,1% in the total group of patients. The mutations were found only in tumor tissues of men. 75% of mutations carriers are smokers. Analysis of KRAS gene mutations in association with the development of a specific histological type of lung cancer showed that mutations are more common in patients with AC (5,9%) than in patients with SCC (2,2%).

      Conclusion:
      Thus, in the researched group of patients mutations in the EGFR gene were found only among non-smoking women with AC, mutations in the EGFR gene were detected only among men independently of histological type of NSCLC.

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    P2.02 - Poster Session with Presenters Present (ID 462)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P2.02-002 - Association between VEGF Gene Functional Polymorphisms and Clinical and Pathological Characteristics of Non-Small Cell Lung Cancer (ID 4111)

      14:30 - 14:30  |  Author(s): A. Mikhalenka

      • Abstract

      Background:
      Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factor, which promotes endothelial cell growth and tumor neovascularization. VEGF expression is a marker of invasiveness and tumor progression in various cancers including in NSCLC. The aim of this study was to analyze association between VEGF gene functional polymorphisms and clinical and pathological characteristics of NSCLC.

      Methods:
      A total of 276 people with histological diagnosis of squamous cell carcinoma (SCC) and adenocarcinoma (AC) were included in this study. All patients gave their informed consent. VEGF gene polymorphisms were determined by PCR-RFLP analysis. Statistical analysis of the material was carried out using SNPStats online program.

      Results:
      Analysis of rs699947 polymorphism association with clinical and pathological characteristics of the tumor showed that patients with -2578CC genotype are more likely to have a greater extent of the primary tumor (T2-T4) than a small non-invasive cancer (T1): p = 0.005; OR = 2.54, 95% CI: 1.35-4.77. Association between this polymorphism and regional lymph node metastasis and the stage of the disease was found. A-allele is protective against a more aggressive course of the disease: in patients with -2578AA genotype regional lymph node metastases (N1-3) occur less frequently as compared to -2578CC genotype carriers (p = 0.0098; OR = 0.34, 95% CI: 0.17-0.69). -2578A-allele carriers are less likely to have stages of the disease III and IV (p = 0.012 and 0.015 respectively). A tendency of rs3025039 polymorphism influence on the histological type of the tumor was identified. + 936TT genotype is more common in patients with SCC as compared to AC (p = 0.055; OR = 4.78, 95% CI: 1.01-22.71). For rs2010963 polymorphism the association with clinical and pathological characteristics of NSCLC was not identified. Haplotype analysis of three studied polymorphisms of VEGF gene showed a significant association between -634C/-2578C/+936C haplotype and a small non-invasive cancer (p = 0.0068). -634G/-2578C/+936C haplotype carriers showed high aggressiveness of the disease (stage - p = 0.0061; regional lymph node metastasis - p= 0.0014).

      Conclusion:
      -2578CC genotype of rs699947 polymorphism VEGF gene is associated with a large size of the primary tumor focus, the occurrence of regional lymph node metastasis and a greater stage of the disease. High aggressiveness of the disease was revealed in -634G/-2578C/+936C haplotype carriers. A significant association between -634C/-2578C/+936C haplotype and small non-invasive cancer was showed.