Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

S. Park



Author of

  • +

    MO10 - Molecular Pathology II (ID 127)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
    • +

      MO10.11 - Genetic polymorphisms of TERT and TP63 genes are associated with exon 18 and exon 21 mutations of EGFR in adenocarcinoma of the lung. (ID 3046)

      17:15 - 17:20  |  Author(s): S. Park

      • Abstract
      • Presentation
      • Slides

      Background
      The presence of mutations of epidermal growth factor receptor (EGFR) is related to phenotypical characteristics such as ethnicity, gender and smoking status. Such observations led us to explore associations between genetic polymorphisms and EGFR mutational status.

      Methods
      We set up a set of samples from 677 primary pulmonary adenocarcinoma. We tested two genetic polymorphisms (rs2736100 and rs10937405), which were discovered previously as to be associated with the risk of lung adenocarcinoma. The association between EGFR mutational status and genetic polymorphisms were evaluated using logistic regression analysis.

      Results
      In 673 patients, four exons (18, 19, 20, 21) of EGFR were completely evaluated. Presence of EGFR mutations were found in 382 (56.8%) patients. In logistic regression analysis, female gender (aOR, 1.7 with 95% CI, 1.0-2.9) and smoking status (ex-smoker, aOR, 0.6 with 95% CI, 0.4-1.1; current smoker aOR, 0.4 with 95% CI, 0.2-0.8) were associated with presence of EGFR mutations. None of two single nucleotide polymorphism (SNP) sites showed significant association. In the analysis of individual type of EGFR mutations, however, we found a significant association between EGFR exon 18 mutations and a SNP rs27366100T/G located in TERT. The G/G genotype showed a 2.8-fold increase in the occurrence of the EGFR exon 18 mutations compared to T/T+G/T genotypes (aOR, 2.8 with 95% CI, 1.2-8.7). Additionally, C/T+T/T genotypes of rs10937405C/T SNP in TP63 showed frequnt occurrences of EGFR exon 21 mutations compared to CC genotype (aOR, 1.5 with 95% CI, 1.0-2.3).

      Conclusion
      Our findings suggest that the somatic mutations of EGFR may be closely associated with genetic polymorphisms. Further investigation of this field may enable us to identify patients who may get a benefit from EGFR inhibitors.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P2.07 - Poster Session 2 - Surgery (ID 190)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
    • +

      P2.07-013 - Risk factors for locoregional failure in completely resected N1 non-small cell lung cancer without postoperative radiotherapy (ID 1316)

      09:30 - 09:30  |  Author(s): S. Park

      • Abstract

      Background
      N1 disease is a subset of non-small cell lung cancer (NSCLC) with a different prognosis than other subsets. Although the NCCN guideline recommends adjuvant chemotherapy alone in completely resected N1 disease, locoregional failure, which could have been prevented by postoperative radiotherapy (PORT), may not be uncommon. Using PORT with modern techniques has resulted in significantly higher rates of local control, disease-free survival, and overall survival. Therefore, this study aimed to evaluate the actuarial rates of locoregional failure in patients with pathologic N1 NSCLC and to identify the risk factors associated with an increased risk of locoregional failure, which could have been potentially prevented by PORT after complete resection.

      Methods
      Between 2003 and 2010, we enrolled 136 patients who underwent complete resection with pathologically confirmed N1 disease through the prospective lung cancer database of Seoul National University Bundang Hospital. Patients who underwent neoadjuvant therapy, adjuvant radiotherapy, or operative mortality were excluded. Multiple factors potentially related to outcomes including patient-related factors, surgery-related factors, and pathologic factors were extensively evaluated. Locoregional failure, which could have been potentially prevented by PORT, was defined as recurrence at either a bronchial stump, or a resected margin of the lung, hilum, and mediastinum. Other failures were ipsilateral lung recurrence, pleural seeding, and metastasis of distant organs. Univariate analysis by a log rank test and multivariate analysis by the Cox proportional hazards model were performed to identify risk factors independently associated with a higher risk of locoregional failure.

      Results
      The median follow-up duration was 45 months (6-114) and recurrence developed in 54 (40%) patients. The actuarial 5-year rates of disease-free survival and overall survival were 56% and 66%, respectively. From the perspective of first site recurrence, 23 (17%) locoregional failures, which could have been potentially prevented by PORT, included recurrence in the mediastinum in 10, bronchial stump in 5, regional lymph nodes in 4, and mediastinum + others in 4. The 31 (23%) other failures included a distant organ in 17, ipsilateral lung in 12, and pleural seeding in 2. The median survival time from locoregional failure and other failures was 41 and 57 months, respectively; however, there was no significant difference. Risk factors of locoregional failure were squamous cell carcinoma, number of involved node (>1), pathologic stage (IIIA), interlobar node involvement, more than 2 node stations of involvement, and a lymph node ratio greater than 10% by univariate analysis. Pathologic stage (HR=4.768, 95% CI=1.641-13.859, p=0.01), interlobar node involvement (HR=2.783, 95% CI=1.057-7.327, p=0.04), and squamous cell carcinoma (HR=2.449, 95% CI=0.929-6.454, p=0.07) were independent risk factors by multivariate analysis.

      Conclusion
      Locoregional failure was more common than expected, and pathologic stage, interlobar node involvement, and cell type were independent risk factors for locoregional failure after complete resection of N1 NSCLC. A prospective clinical trial may be necessary to evaluate the effectiveness of adjuvant radiotherapy in patients with these risk factors.

  • +

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
    • +

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

      09:30 - 09:30  |  Author(s): S. Park

      • 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.