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T. Takuwa



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    P1.14 - Poster Session 1 - Mesothelioma (ID 194)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P1.14-012 - Activation of mTOR signal pathway is associated with prolonged survival in malignant pleural mesothelioma patients (ID 2715)

      09:30 - 09:30  |  Author(s): T. Takuwa

      • Abstract

      Background
      Malignant Pleural Mesothelioma (MPM) is a rare disease with poor prognosis. The combination chemotherapy with cisplatin and pemetrexed is the first line of MPM. The AKT/mTOR (Mammalian Target of Rapamycin) pathways are known to be activated in some kind of cancer. The purpose of this study is to evaluate the correlation between the activation of these pathways and prognosis of MPM patients.

      Methods
      46 patients with MPM underwent a multimodality therapy including extrapleural pneumonectomy (EPP) at Hyogo College of Medicine, Nishinomiya, Japan from April 2004 to October 2012. The 46 cases included 35 males (76.0%) and 11 females (23.9%). Median Ages is 59.8 (ranged from 37 to 71 years). Histologic subtype is 42 epithelial type (91.3%), 2 biphasic type (4.3%), 1 desmoplastic type (2.1%), 1 small cell type (2.1%). Paraffin embedded surgical sample was used for immunohistochemistry to evaluate the expression of phospho- mTOR (p-mTOR) and phospho-S6 Ribosomal Protein (p-S6RP). Overall survival (OS) from the time of surgery was determined by Kaplan-Meier method and results were compared by log-rank test.

      Results
      OS was significantly better in phospho-S6RP positive patients (32/46) in comparative with phosphor-S6RP negative patients (14/46) (43.6 months vs. 14.4 months, P=0.03). OS was significantly better in phospho-mTOR positive patients (18/46) in comparative with phosphor-mTOR negative patients (28/46) (37.1 months vs. 14.4 months, P=0.08).

      Conclusion
      In MPM patients, high phospho-S6RP expression is predictive of improved OS. The assessment of phospho-S6RP expression is worth of prospective validation in future studies on a multimodality therapy of MPM. And this study support that the AKT/mTOR pathways is a promising candidate of molecular target therapy for MPM.

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-050 - Characteristic Immunophenotype of Solid Subtype Component<br /> in Lung Adenocarcinoma (ID 3289)

      09:30 - 09:30  |  Author(s): T. Takuwa

      • Abstract

      Background
      Lung adenocarcinomas represent a morphologically heterogeneous tumor composed of an admixture of different histologic subtypes (lepidic, papillary, acinar, and solid subtype). The presence of a solid subtype component is reported to be associated with a poorer prognosis. The aim of this study was to evaluate the characteristic immunophenotype of the solid subtype component compared with the immunophenotypes of other components.

      Methods
      We analyzed the clinicopathological characteristics of stage I adenocarcinoma patients with predominant solid subtype disease. Furthermore, we immunostained adenocarcinomas with predominant lepidic, papillary, acinar, and solid subtype components (n = 23 each) for 10 molecular markers of tumor invasiveness and scored the results.

      Results
      Patients showing predominance of the solid subtype component (solid subtype adenocarcinoma) had a poorer prognosis than those showing predominance of the lepidic, papillary, or acinar component. Lymphovascular invasion was more often detected in solid subtype tumors than in others. The solid subtype component showed a significantly stronger staining intensity of laminin-5 expression than the lepidic, papillary, and acinar components (P\\0.001, P\\0.001, and P = 0.016, respectively). The fibronectin and vimentin expression levels were also significantly higher in the solid subtype component than in other components. This immunostaining character was validated by using mixed-subtype adenocarcinomas containing all four components in the same tumor.

      Conclusion
      This study concluded that the solid subtype component in lung adenocarcinomas exhibit the invasive immunophenotype, including increased laminin-5 expression, compared with the other components, which may be associated with a poorer prognosis.