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T. Nagashima



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    OA10 - EGFR Mutations (ID 382)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
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      OA10.02 - Association of Variations in HLA-Class II and Other Loci with Susceptibility to EGFR-Mutated Lung Adenocarcinoma (ID 4192)

      11:00 - 12:30  |  Author(s): T. Nagashima

      • Abstract
      • Presentation
      • Slides

      Background:
      Lung adenocarcinoma (LADC) driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Understanding the genetic factors underlying such LADC is required to elucidate disease etiology and to identify effective methods of prevention.

      Methods:
      We investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls.

      Results:
      Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2, HLA-class II), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA-class II at 6p21.32 and 6p21.1 (FOXP4) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma (Shiraishi et al., Nature Communications, 2016, in press).

      Conclusion:
      This study indicates that multiple genetic factors, including an immunologic one, underlie the risk of lung adenocarcinomas with EGFR mutations.

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    P2.01 - Poster Session with Presenters Present (ID 461)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.01-030 - Prognostic Impact of Stathmin1 Expression in Patients with Non-Small Lung Cancer (ID 4843)

      14:30 - 15:45  |  Author(s): T. Nagashima

      • Abstract
      • Slides

      Background:
      Stathmin 1 is a cytosolic phosphoprotein that plays a crucial role in the control of cellular division and proliferation by regulating microtubule dynamics. In addition, Stathmin1 is associated with tumor growth and progression. Our study aimed to determine differences in overall (OS) and disease free survival (DFS) in patients with non-small lung cancer (NSCLC) stratified by STMN1 tumor expression.

      Methods:
      Using inmmunohistochemistry, Stathmin1 expression was determined in resection specimens from 423 NSCLC patients. The relationship between Stathmin1 protein expression and overall and disease free survivalwas assessed using Kaplan Meier survival curves and compared using log-rank statistics. Cox proportional hazards regression determined the hazard for death stratified by Stathmin1, adjusting for clnicopathological characteristics.

      Results:
      The STMN1 protein was expressed in 58% of NSCLC cases, 54% of Adenocarcinoma, 63% of Squamous cell carcinoma, and 100% of large cell neuroendocrine carcinoma (LCNEC) and its expression was significantly associated with advanced T and N factors, advanced pathological stages, positive lymphatic permeation, positive vascular invasion, and poor or mediate differentiation. STMN1 was a negative prognostic factor for OS (hazard ratio [HR], 2.212; 95% confidence interval [CI]: 1.544-3.169; p< 0.001) and DFS (HR, 2.685; 95% CI: 1.897-3.798; p< 0.001). Multivariable analysis confirmed that STMN1 protein expression was an independent predictor of an unfavorable OS (HR, 1.480; 95% CI, 1.006 to 2.176; p = 0.046) and DFS (HR, 1.605; 95% CI, 1.105 to 2.329; p = 0.013) in all NSCLC patients, and of an unfavorable DFS (HR: 2.128, 95% CI, 1.293 to 3.503; p = 0.003) in Stage I NSCLC patients.

      Conclusion:
      STMN1 expression was an independent prognostic factor for NSCLC, even when restricted to early stage patients.

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