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Yuko Minami



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    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.09-24 - IASLC Global Survey for Pathologists on PD-L1 Testing for Non-Small Cell Lung Cancer (ID 906)

      10:15 - 18:15  |  Author(s): Yuko Minami

      • Abstract
      • Slides

      Background

      PD-L1 immunohistochemistry (IHC) is now performed for advanced non-small cell lung cancer (NSCLC) patients to examine their eligibility for pembrolizumab treatment, as well as in Europe for durvalumab therapy after chemoradiation for stage III NSCLC patients. Four PD-L1 clinical trial validated assays (commercial assays) have been FDA/EMA approved or are in vitro diagnostic tests in multiple countries, but high running costs have limited their use; thus, many laboratories utilize laboratory-developed tests (LDTs). Overall, the PD-L1 testing seems to be diversely implemented across different countries as well as across different laboratories.

      Method

      The Immune biomarker working group of the IASLC international pathology panel conducted an international online survey for pathologists on PD-L1 IHC testing for NSCLC patients from 2/1/2019 to 5/31/2019. The goal of the survey was to assess the current prevalence and practice of the PD-L1 testing and to identify issues to improve the practice globally. The survey included more than 20 questions on pre-analytical, analytical and post-analytical aspects of the PDL1 IHC testing, including the availability/type of PD-L1 IHC assay(s) as well as the attendance at a training course(s) and participation in a quality assurance program(s).

      Result

      344 pathologists from 310 institutions in 64 countries participated in the survey. Of those, 38% were from Europe (France 13%), 23% from North America (US 17%) and 17% from Asia. 53% practice thoracic pathology and 36%, cytopathology. 11 pathologists from 10 countries do not perform PD-L1 IHC and 7.6% send out to outside facility. Cell blocks are used by 75% of the participants and cytology smear by 9.9% along with biopsies and surgical specimens. Pre-analytical conditions are not recorded in 45% of the institutions. Clone 22C3 is the most frequently used (61.5%) (59% with the commercial assay; 41% with LDT) followed by clone SP263 (45%) (71% with the commercial assay; 29% with LDT). Overall, one or several LDTs are used by 57% of the participants. A half of the participants reported turnaround time as 2 days or less, while 13% reported it as 5 days or more. Importantly, 20% of the participants reported no quality assessment, 15%, no formal training session for PD-L1interpretation and 14%, no standardized reporting system.

      Conclusion

      There is marked heterogeneity in PD-L1 testing practice across individual laboratories. In addition, the significant minority reported a lack of quality assurance, formal training and/or standardized reporting system that need to be established to improve the PD-L1 testing practice globally.

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    P2.11 - Screening and Early Detection (ID 178)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.11-34 - Application of Next-Generation Sequencing for Screening of Sputum Samples (Now Available) (ID 1246)

      10:15 - 18:15  |  Presenting Author(s): Yuko Minami

      • Abstract
      • Slides

      Background

      Since the efficiency of CT mass-screening was reported in NEJM in 2013, many countries have been actively adopting CT screening for detection of lung cancers, especially peripheral-type lung adenocarcinoma. On the other hand, another mass-screening method, “sputum cytology”, has a very low cancer detection rate and its use has been decreasing worldwide. Nevertheless, sputum is one of the easiest types of sample to collect from patients, and sputum samples are thought to contain not only cancer cells, but also cancer cell-free DNA.The present study examined genomic abnormalities in DNA contained in sputum, and investigated the efficiency of next-generation sequencing (NGS) for detection of lung cancer or identifying patients at high risk.

      Method

      Using the Saccomanno method, we collected sputum samples from 15 patients (5 with squamous cell carcinoma, 5 with adenocarcinoma, and 5 with non-neoplastic conditions). A 1500 μl volume of each sample was centrifuged, and the sediment was resuspended in 180 μl of supernatant. After incubation with protease K at 56ºC for 90 min, DNA was extracted using MagLead 6GC (Precision System Science Co., Ltd., Japan). All DNA samples were subjected to NGS using Ion AmpliSeq Cancer Hotspot Panel v2 (Thermo Fisher Scientific, USA).

      Result

      The median age of the patients overall was 71 years (range, 56–94 years), and that of patients with squamous cell carcinomas, adenocarcinomas and non-neoplastic conditions was 66 years (64-78), 71 years (67-73) and 86 years (56-94), respectively. HRAS and p53 mutations were found only in cancer patients (HRAS 2/10, p53 4/10). There were no significant differences in mutation pattern between squamous cell carcinoma and adenocarcinoma patients. Although mutations of ALK, PIK3CA, PTEN, KRAS, FLT3, and RB1 were frequently found in samples from cancer patients (ALK 5/10, PIK3CA 5/10, PTEN 7/10, KRAS 7/10, FLT3 4/10, and RB1 8/10), such mutations were also present in non-neoplastic conditions. Mutations at the same locus in ALK, PIK3CA, PTEN and RB1 were also found in non-neoplastic conditions (ALK 1/5, PIK3CA 1/5, PTEN 2/5, and RB1 1/5). Seventeen out of 48 gene mutations were found only in non-neoplastic conditions.

      Conclusion

      Detectable mutation patterns differed between cancer and non-neoplastic conditions, but were similar between squamous cell carcinoma and adenocarcinoma. Validation tests will be performed on DNA extracted from more than 400 sputum samples.

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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-22 - Loss of Ect2 Expression Impairs Cell-Matrix Adhesion and FAK/Src Signaling in Lung Adenocarcinoma Cells (ID 192)

      10:15 - 18:15  |  Author(s): Yuko Minami

      • Abstract
      • Slides

      Background

      Cell adhesion is a crucial step in cancer development and progression. We have previously demonstrated that epithelial cell transforming sequence 2 (Ect2), a guanine nucleotide exchange factor for the Rho family small GTPases Rac1, RhoA, and Cdc42, is overexpressed in early invasive adenocarcinoma. We subsequently showed that suppression of Ect2 significantly reduces cell growth, migration, and invasion of lung adenocarcinoma cells. In the present study, we investigated the potential role of Ect2 on cell-matrix adhesion and adhesion signaling complex in lung adenocarcinoma.

      Method

      Cell attachment assay was used to assess the viability of attached Calu-3 and PC-9 cells after suppression of Ect2 using small interfering RNA (siRNA). Adhesion of cells to extracellular matrix (ECM) was examined by adhesion assay, and changes in cell morphology were observed by immunofluorescence. RT-PCR and Western blotting analysis were conducted to examine the effects of Ect2 suppression on molecules involved in the adhesion cascade in Calu-3 and NCI-H2342 cells. To evaluate the effect of Ect2 on adhesion complex formation, immunoprecipitation was performed after treatment with siRNA-Ect2 in Calu-3 cells.

      Result

      We found that suppression of Ect2 significantly reduced the viability of attached cells. Furthermore, PC-9 and Calu-3 cells transfected with siRNA-Ect2 showed markedly decreased adhesion to collagen I and fibronectin. In terms of morphological changes, Calu-3 and PC-9 cells showed non-cohesive growth and a clear rounded shape after siRNA-Ect2 treatment. To investigate the underlying molecular mechanism, we examined the levels of expression of several proteins that are directly associated with cancer cell adhesion. We found that focal adhesion kinase (FAK), a key regulator of cell adhesion, was markedly down-regulated at both the mRNA and protein levels after treatment of the lung adenocarcinoma cells with siRNA-Ect2. Consistently, the levels of expression of molecules involved in the adhesion cascade, including integrin β1, paxillin, p-Src (Tyr416), p130Cas, and Crk, were further decreased in siRNA-Ect2. Since FAK/Src signaling can be activated through interaction the adhesion molecules on the cell surface, we speculate that these interactions might be affected by Ect2. Our data showed that Ect2 suppression impairs FAK interaction with Src, integrin β1, and paxillin in lung adenocarcinoma cells.

      Conclusion

      We have obtained novel data suggesting that Ect2 suppression leads to attenuation of cell adhesion to ECM, with a consequent impact on adhesion complex formation. These findings further demonstrate that Ect2 plays an essential role in the pathological steps of lung adenocarcinoma progression, and could be a potential molecular target for therapy.

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