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Masahiro Tsuboi



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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-25 - Abundant Tumor Promoting Stromal Cells in Lung Adenocarcinoma with Hypoxic Regions (ID 12409)

      16:45 - 18:00  |  Author(s): Masahiro Tsuboi

      • Abstract
      • Slides

      Background

      Carbonic anhydrase IX (CAIX) is a marker of hypoxia and its expression by cancer associated fibroblasts (CAFs) was reportedly associated with the poor prognosis of lung adenocarcinoma. This study aimed to characterize the hypoxic microenvironment containing CAIX (+) CAFs.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      First, we evaluated the clinicopathological significance of CAIX expression by CAFs in 3 cm and above lung adenocarcinoma (n = 188). We then compared the expressions of E-cadherin, ezrin, ALDH1, CD44, EGFR, HSF-1, Glut-1, and PD-L1 in cancer cells, as well as those of CD204 and podoplanin in stromal cells between CAIX (+) CAFs and CAIX (−) CAFs cases (n = 25, each).

      4c3880bb027f159e801041b1021e88e8 Result

      In total, 48 patients had CAIX (+) CAFs (26%). Multivariate analysis revealed that CAIX expression by CAFs could serve as an independent unfavorable prognostic factor for recurrence-free survival (p < 0.05). The staining score of hypoxia marker Glut-1 in cancer cells was significantly higher in cases with CAIX (+) CAFs than in those with CAIX (−) CAFs (median: 20 vs. 0, p < 0.01). In addition, the numbers of CD204 (+) tumor associated macrophages (TAMs) and podoplanin (+) CAFs were significantly higher in the CAIX (+) CAFs group than in the CAIX (−) CAFs group (TAMs: 31.5 vs. 17.0: p < 0.01, CAFs: 20 vs. 0: p < 0.05). The staining score of the other markers did not differ between the groups.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results indicate that the presence of abundant tumor promoting stromal cells, CD204 (+) TAMs, and podoplanin (+) CAFs is characteristic of the tumor microenvironment containing CAIX (+) CAFs, which contributes to an increase in aggressive behavior in lung adenocarcinoma with hypoxic regions.

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    P3.09 - Pathology (Not CME Accredited Session) (ID 975)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.09-06 - The Link Between Tumor Promoting Fibrous Microenvironment and Immunosuppressive Microenvironment in Stage I Lung Adenocarcinoma (ID 14371)

      12:00 - 13:30  |  Author(s): Masahiro Tsuboi

      • Abstract
      • Slides

      Background

      Podoplanin-positive cancer-associated fibroblasts (PDPN (+)CAFs) play an important role in cancer progression in non-small-cell lung cancer (NSCLC). The aim of this study is to clarify the correlation between fibrous microenvironment containing PDPN (+) CAFs and immune microenvironment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      174 cases with stage I primary lung adenocarcinoma were analyzed in this study. We evaluated PDPN (+) CAFs and immune-related cells; CD 204-positive tumor-associated macrophages (CD204 (+) TAMs); CD8-positive T cells; and FOXP3-positive T cells in cancer stroma by immunohistochemical staining method. By analyzing the gene expression profiles of lung adenocarcinoma (n=442), we compared the expression level of immune-regulatory cytokines between PDPN expression-high group and PDPN expression-low group.

      4c3880bb027f159e801041b1021e88e8 Result

      Presence of PDPN (+) CAFs was a risk factor for recurrence (P = 0.012). The number of CD204 (+) TAMs was significantly higher in PDPN (+) CAFs cases than in PDPN (+) CAFs cases (P < 0.001). Furthermore, CD8 (+)/FOXP3 (+) T cell ratio was significantly lower in PDPN (+) CAFs cases (P = 0.027). Within the same tumor, the number of CD 204 (+) TAMs was significantly higher in PDPN (+) CAFs area than in PDPN (-) CAFs area (P < 0.001). Moreover, CD8 (+)/FOXP3 (+) T cell ratio tend to be lower in PDPN (+) CAFs area than in PDPN (+) CAFs area (P = 0.062). Microarray analysis revealed PDPN expression-high group had significant higher levels of M-CSF; a cytokine inducing M2 macrophage polarization, and TGFβ1, IDO, VEGFA and galectin 1; immunosuppressive cytokines.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The current results revealed that lung adenocarcinoma with PDPN (+) CAFs is typified by an immunosuppressive microenvironment, suggesting the close link between tumor promoting fibrous microenvironment and immune microenvironment.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.16-40 - Delayed Cut-End Recurrence After Wedge Resection for Pulmonary Ground-Glass Opacity Adenocarcinoma  (ID 11958)

      12:00 - 13:30  |  Author(s): Masahiro Tsuboi

      • Abstract

      Background

      Most pulmonary ground-glass opacity (GGO) nodules indicated by high resolution computed tomography (HRCT) are pathologically well differentiated adenocarcinomas.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed a limited resection trial of GGO lesions 2cm or smaller from 2003 to 2009, in which accumulated 95 patients were included. The lesion had to be a pure or mixed GGO nodule with a tumor disappearance ratio of 0.5 or greater on HRCT. We confirmed negative surgical cut-end during surgery by margin lavage cytology. Case: In the trial, a 51-year-old man underwent right lower lobe wedge resection for a 1.7 cm mixed GGO lesion. The tumor was papillary predominant adenocarcinoma, pT1NxM0. The resection scar started to become thicker 8 years after the initial surgery. When the lesion grew larger at 10 years, it was diagnosed as adenocarcinoma by needle biopsy. We performed a right lower lobectomy and lymph node dissection.

      4c3880bb027f159e801041b1021e88e8 Result

      Pathologically, the second tumor was adenocarcinoma similar to the initial one, papillary predominant with lepidic and acinar components. No pleural or vessel invasion was identified, and there were no nodal metastases. Cut-end staples and sutures used during the initial surgery to control air leakage were identified within the tumor. Genetically, 2 specimens from the initially resected GGO adenocarcinoma were studied and showed no epidermal growth factor receptor (EGFR) gene mutation or echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene. A needle biopsy specimen from the second adenocarcinoma also had no EGFR mutation or EML4-ALK fusion gene, however, the lobectomy specimen had EGFR mutation (L858R in exon21).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Small papillary-predominant adenocarcinoma might develop delayed cut-end recurrence more than 5 years after limited resection. Careful follow-up with special attention to the cut-end[S1] is necessary ideally for 10 years.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    SH01 - Highlight of the Previous Day Sessions (ID 884)

    • Event: WCLC 2018
    • Type: Highlight of the Day Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 07:00 - 08:00, Plenary Hall
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      SH01.02 - Surgery (ID 14777)

      07:00 - 07:12  |  Presenting Author(s): Masahiro Tsuboi

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    VPS2020 - WCLC 2020 - Virtual Presidential Symposium

    • Event: WCLC 2020 - Virtual Presidential Symposium
    • Type: Online Presentation
    • Track: N.A.
    • Presentations: 1
    • Moderators:
    • Coordinates: 8/19/2020, 08:00 - 17:00,
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      Educational Talk 1 - Peri-operative Adjuvant IO or TKIs Therapy for Resected NSCLC

      08:00 - 17:00  |  Presenting Author(s): Masahiro Tsuboi

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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