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T. Shima



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    OA10 - EGFR Mutations (ID 382)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
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      OA10.05 - EGFR Gene Mutations Affect Tumor-Infiltrating Stromal Cell Components in Early-Stage Lung Adenocarcinoma (ID 6305)

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

      • Abstract
      • Presentation
      • Slides

      Background:
      Tumors are complex structures consisting of cancer cells surrounded by a tumor stroma that is now recognized to be critical for cancer progression. Although epidermal growth factor receptor (EGFR) mutations are frequently observed in non-small cell lung carcinoma, it remains poorly understood whether EGFR mutations in cancer cells affect the tumor stroma. In this study, we studied the status of EGFR mutations in early-stage lung adenocarcinoma and analyzed the relations of EGFR mutations to tumor-infiltrating stromal cell components.

      Methods:
      A total of 152 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete tumor resection in Keio University Hospital between 2010 and 2014 were studied. Genomic DNA was isolated from formalin-fixed, paraffin-embedded tumor sections and mutational analyses of EGFR gene exons 19, 20 and 21 were performed by a polymerase chain reaction-based method. Paraffin sections were also subjected to immunohistochemistry for CD3, FOXP3, CD163 or CD204. Numbers of CD3-, FOXP3-, CD163- or CD204-immunostained cells were counted by observing 5 different fields at x200 magnification.

      Results:
      EGFR mutations were detected in 71 (47%) of the 152 patients with clinical stage IA lung adenocarcinoma and were found more frequently in women and non-smokers. These contained 38 patients with missense mutations in exon 21 (L858R) and 30 patients with deletions in exon 19. By immunohistochemistry, the number of stromal macrophages positive for CD163 or CD204, markers for tumor-associated macrophages (TAMs), was significantly decreased within tumors with EGFR mutations compared to within those with wild-type EGFR, whereas the number of CD3[+] T cells or FOXP3[+] regulatory T cells was comparable between these groups. Both tumors with missense mutations in exon 21 and deletions in exon 19 had a similar trend toward decreased TAMs in the tumor stroma.

      Conclusion:
      Our data suggest that EGFR mutations in early-stage lung adenocarcinoma are associated with decreased TAMs in the tumor stroma. EGFR mutation status might act on not only cancer cell behavior but tumor microenvironment.

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    P2.04 - Poster Session with Presenters Present (ID 466)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      P2.04-016 - Is FDG-PET Useful for Distinguishing between Thymic Epithelial Tumors and Malignant Lymphoma? (ID 5234)

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

      • Abstract

      Background:
      It is difficult to diagnose the tumor in the anterior mediastinum by computed tomography. Distinguishing between thymic epithelial tumors and malignant lymphoma is important, because therapeutic strategy is difficult in each disease. The objective of this study was to clarify the usefulness of positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) for distinguishing thymic epithelial tumors and malignant lymphoma.

      Methods:
      We retrospectively reviewed FDG PET-CT scans of 42 patients pathologically diagnosed by surgery or biopsy as thymic epithelial tumors or malignant lymphoma. FDG uptake was measured as the maximum standard uptake value (SUVmax). Student t tests were used to assess association between SUVmax and pathological diagnosis.

      Results:
      Among the 42 patients, 26 patients had a pathological diagnosis of thymoma: WHO classification type A in 3 patients (11%), type AB in 5 patients (19%), type B1 in 10 patients (19%), type B2 in 11 patients (42%), and type B3 in 2 patients (7%). Eight patients had the thymic carcinoma. Eight patients had the malignant lymphoma. The SUVmax in malignant lymphoma (13.4±6.3) was significantly higher than that in the thymic epithelial tumors (4.9±2.4) (p<0.001). The SUVmax in thymic carcinoma (7.9±3.0) was higher than that in the thymoma (4.5±1.3) (p=0.002) . The ROC curve of SUVmax for predicting malignant lymphoma indicated that the optimal cutoff value was 7.3. This value had a sensitivity of 0.88 and a specificity of 0.99 (area under curve, 0.93).

      Conclusion:
      FDG PET-CT is helpful for distinguishing malignant lymphoma from thymic epithelial tumors with cut off value of 7.3.