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  P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 15415

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    P3.04-033 - Screening for Driver Mutations in Caucasian Patients with Central Nervous System Metastases of Non-Small-Cell Lung Cancer (ID 1047)

    09:30 - 09:30  |  Author(s): B. Jarosz
    • Abstract
    • Slides

    Background:
    The knowledge about molecular profile of advanced NSCLC may increase the possibility and effectiveness of cancer treatment. According to data of LCMC, FNN and CRUK, driver mutations are reported in 50-60% of non-small cell lung cancer (NSCLC) patients, especially in adenocarcinoma subtype. Unfortunately, we have limited information concerning the incidence of driver mutations in metastatic lesions of NSCLC. The main aim of the study was characterize the molecular background of central nervous system (CNS) metastatic lesions of NSCLC. It was performed by estimation the frequency of selected driver mutations in Caucasian chemotherapy and molecularly targeted therapy naïve patients.
    
    Methods:
    The studied group included 145 patients (45 females, 100 males, age: 60±8,8 years) with CNS metastases of NSCLC.The studied group included 80 adenocarcinomas, 29 squamous-cell carcinomas, 22 large-cell carcinomas and 14 not otherwise specified patients. 36 patients were non-smokers. In 30 patients the material was simultaneously available from primary and metastatic NSCLC tumors. The molecular profile of driver mutations was determined in EGFR, KRAS, NRAS, BRAF, PIK3CA, HER2, and DDR2 genes. Mutations were screened in DNA isolated from formalin-fixed paraffin-embedded tissue samples using the quantitative real-time PCR technique with commercially available molecular kits. The driver mutations presence was confirmed by DNA sequencing, multiple single-strand conformation polymorphism (MSCCP) and other PCR techniques.
    
    Results:
    The driver mutations were identified in 52/145 (36%) of patients with CNS metastases (Fig.1), significantly more frequent in adenocarcinoma (p= 0.05, χ[2]= 3.817), patients and non-smokers (p= 0.004, χ[2]= 8.131). Only one patient had doublet mutations in DDR2 and KRAS genes. In corresponding primary tumors we detected 10/30 (33%) mutations in KRAS gene (7/30, 23%) and EGFR gene (3/30, 10%). However, 5 KRAS mutations were identified both in primary and metastatic lesions, while 1 mutation was detected only in primary tumor and 1 mutation - only in the metastatic tumor.
    
    Conclusion:
    Analysis of molecular profile confirmed assumptions that driver mutations could be detected both in primary and CNS metastatic tumors of NSCLC. Therefore, both primary and metastatic tumor samples could be considered as a representative for molecular testing in patients with metastatic cancer. Figure 1
    
    
    
    

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