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A. Yoshida



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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): A. Yoshida

      • 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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    P3.01 - Poster Session with Presenters Present (ID 469)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P3.01-015 - Prognostic Impact of Histologic Invasion Factors in Pulmonary Adenocarcinoma, with Particular Focus on the Pattern of Architectural Remodeling (ID 4975)

      14:30 - 15:45  |  Author(s): A. Yoshida

      • Abstract
      • Slides

      Background:
      In the 2015 WHO classification, histologic factors that are associated with invasion in primary lung adenocarcinoma (AdCa) include the presence of non-lepidic histologic subtypes (invasive subtypes) and the presence of cancer-associated myofibroblasts (CAFs). The prognostic significance of CAFs in combination with each invasive subtype has not been well assessed. We conducted this study to clarify the prognostic impact of CAFs in the absence of architectural remodeling.

      Methods:
      We retrospectively collected data and re-evaluated samples from 1052 patients with pathological stage 0 or IA pulmonary AdCa who underwent complete resection at our hospital between 2007 and 2012. HE and elastica van Gieson stains were used for histological evaluation. We defined two invasive subtypes: those with (INV-1) and without (INV-2) architectural remodeling of lung parenchyma. The postoperative recurrence of tumor was analyzed in each group.

      Results:
      Our reviewed diagnoses were 172 Stage 0 and 880 Stage IA AdCa. Of the 880 stage IA cases, 706 (80.2%) and 174 (19.8%) were categorized as INV-1 and INV-2, respectively. CAFs were observed in all cases in the INV-2 group, but were not always present in the INV-1 group. In the INV-2 group, the median diameter of the invasive component was 6 mm (range: 1-16), the median postoperative follow-up period was 60 months (range: 2-105), and none of the cases developed recurrence. In the INV-1 group, the median postoperative follow-up period was 55 months (range: 1-104) and the estimated 5-year recurrence-free probability by the Kaplan-Meier method was 93.0%. All cases with postoperative recurrence were categorized in the INV-1 group.

      Conclusion:
      The INV-2 group AdCa had a low risk of recurrence. These findings suggest that certain subtypes of invasive AdCa, which are classifiable based on the architectural remodeling pattern and the presence of CAF, can be considered to have a good prognosis.

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