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K. Emoto



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    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P3.02-084 - FGF9-FGFR Pathway Induce Neuroendocrine Differentiation in Lung Epithelial Cells (ID 7553)

      09:30 - 09:30  |  Author(s): K. Emoto

      • Abstract
      • Slides

      Background:
      Small cell lung cancer (SCLC), an aggressive and metastatic disease, accounts for about 15% of lung cancer. Neuroendocrine differentiation is essential molecular event in SCLC development. The mechanisms of neuroendocrine differentiation and SCLC development remain elusive. For the improvement of the prognosis of SCLC patients, clarification of the mechanisms of neuroendocrine differentiation is essential.

      Method:
      For in vitro experiments, a stable cell line with constitutive expression of FGF9 in MLE12 (a mouse lung alveolar type II cell line transformed by SV40 large T antigen) was established by retroviral infections (H69: SCLC cell line, MLE12: mouse lung epithelial cell line transformed by SV40). Using these cell lines, the effect of FGF9 on proliferation, colony formation capacity and downstream signaling was evaluated by MTS assay, softagar colony formation assay and Western blotting, respectively. For in vivo experiments, these cell lines were transplanted into the immunodeficient mice subcutaneously, and the size of tumor was measured. To evaluate the efficacy of FGFR inhibitors for FGF9-driven lung cancers, AZD4547, selective FGFR inhibitor, was orally administered. For pathological characterization of the tumors, immunohistochemicalstry staining was performed. For patients study, 31 SCLC samples were obtained and the expression of FGF9 was evaluated by immunohistochemistry.

      Result:
      FGF9 is highly expressed in human SCLC samples (80.6%).FGF9 has oncogenic ability in vitro and its effect may be exerted by the activation of MAPK pathway through FGFR1 and FGFR3 in MLE12 cells. Unexpectedly, pathological analysis revealed FGF9-driven tumors exhibited SCLC histology. FGF9 transforms lung alveolar type II cells to SCLC in vitro and in vivo. Selective FGFR inhibitor, AZD4547 suppressed tumor growth of FGF9-driven MLE12 tumors.

      Conclusion:
      These results suggest that FGF9 has roles of tumor initiation and progression in lung cancer, especially in SCLC. SCLC which highly expresses FGF9 might may be a target of FGFR inhibitors.

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    P3.13 - Radiology/Staging/Screening (ID 729)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P3.13-031 - Predicting Factor for the Dissociation of the Diameter Between Radiographical Solid Part and Pathological Invasive Part in Lung Adenocarcinoma (ID 10184)

      09:30 - 09:30  |  Author(s): K. Emoto

      • Abstract

      Background:
      In part-solid nodule of lung adenocarcinoma, the diameter of the solid part in computed tomography(CT) scan correlates with the diameter of the pathological invasive part. However, there are some cases revealing dissociation between them. We analyzed clinical factors predicting the dissociation of the diameter between radiographical solid part and pathological invasive part in adenocarcinoma less than 3 cm.

      Method:
      Among 291 cases with a lung adenocarcinoma smaller than 3 cm, we identified 91 cases whose solid part in preoperative thin-slice CT scan was less than 5 mm. Based on pathological diagnosis of invasive part, we divided these cases into Adenocarcinoma in situ/Minimally Invasive Adenocarcinoma(AIS/MIA) group (less than 5 mm) and Massive invasion group (5mm or larger), and retrospectively analyzed the clinicopathological factors. We also performed logistic regression analysis to detect the factors predicting the dissociation between radiographical and pathological findings.

      Result:
      Of 91 cases, 67 cases were in AIS/MIA group (AIS: 57, MIA: 10) and 24 cases were in Massive invasion group. In univariative analysis, cases of Massive invasion group were significantly higher in Brinkman index, CEA, age, and total tumor size than those of AIS/MIA group (p = 0.02, 0.01, 0.04, 0.03 respectively). With these detected four factors, we performed logistic regression analysis after determining threshold by ROC curve, which resulted in Brinkman index equal or larger than 400, and age equal or elder than 67 as significant predictive factors for Massive invasion group (p < 0.01, p = 0.05 respectively). Among 11 cases positive for these two factors, 7 cases (63.6 %) were in Massive invasion group.

      Conclusion:
      In the cases of radiographical AIS/MIA, the diameter of pathological invasive part tends to exceed 5 mm if Brinkman index equal or larger than 400, and age equal or elder than 67.