Author of

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  P3.18 - Poster Session 3 - Pathology (ID 177)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12789

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    P3.18-020 - The mutational profile of lung adenocarcinoma in Korean population (ID 3097)

    09:30 - 09:30  |  Author(s): H. Go
    • Abstract

    Background
    Recent development of molecular target agents encouraged us to investigate the presence of driver mutations in patients with non-small cell lung cancer. As the prevalence of individual driver mutation is different in each ethnic group, understanding of mutational profiles of a specific country is important for clinical practice as well as for decision-making process of health care. Hence, we investigated the genetic profile of lung adenocarcinoma in Korean population.

    Methods
    Among the patients who underwent surgical resection for lung adenocarcinoma between 2001 and 2011, we set up a total of 477 patients whose fresh frozen lung cancer tissues and paraffin blocks were available. We retrospectively searched medical records of the EGFR exons 18-21 mutation tests results. Then, we selected patients who did not harbor EGFR mutations or who had not tested for EGFR mutations. DNA was extracted from those patients’ samples, and EGFR exons 18-21 and KRAS mutation test were performed by Sanger sequencing method. Tissue microarray was made for all 477 patients, and the EML4-Alk fusion was tested by a break-apart FISH method. We also tested KIF5B-RET fusion by using a break-apart FISH method and also by inversion specific long-range PCR. We investigated any correlation between mutational status and clinical variables, such as age, gender, smoking status, stage, and long term survivals.

    Results
    Among 477 patients, 321 patients (67.3%) were harboring at least one of four driver mutations. The EGFR mutations were the most frequently detected (270, 56.6%), followed by KRAS mutations (37, 7.8%), and EML4-Alk fusion (19, 4.0%). We also found five patients who had KIF5B-RET fusion mutations (1.0%). There were 10 patients who had more than two driver mutations; EGFR and KRAS mutations in 4, EGFR and EML4-Alk fusion in 4, KRAS and EML4-Alk fusion in one, and EGFR and KIF5B-RET fusion in one patient. The presences of EGFR mutations were frequently observed in patients with female gender (p=0.000). Although the EGFR mutations were associated with longer overall survival in univariate analysis (log-rank test rank test p=0.007), the presence of EGFR mutation was not a prognostic factor in multivariate analysis (Cox’s regression test p=0.469). The mutational statuses were associated with neither the disease-free survival nor fthe reedom from recurrence.

    Conclusion
    Based on our work, we found as high as 67.3% of lung adenocarcinoma patients in Korean populations were harboring at least one driver mutation, which may get a benefit from target agents. We also found as high as 2% of patients harbored multiple driver mutations. As the target agent will eventually develop resistance, it is recommended to test each driver mutation thoroughly even if one driver mutation was detected. Furthermore, our observation suggests future molecular testing should be based on the next generation sequencing platform.