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Anja C Roden



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    OA 03 - Mediastinal and Esophageal Tumor: Insight and New Treatment (ID 654)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      OA 03.06 - Clinicopathologic, Immunophenotypic and Genetic Studies of Mediastinal Paragangliomas (ID 8339)

      11:00 - 12:30  |  Presenting Author(s): Anja C Roden

      • Abstract
      • Presentation
      • Slides

      Background:
      Paragangliomas (PGLs) are rare neuroendocrine neoplasms arising from paraganglia of the autonomic nervous system. Only about 2% of all PGLs are found in the mediastinum; therefore they are not thoroughly investigated. Our study aims to characterize the clinicopathologic, immunophenotypic and genetic features of mediastinal PGLs.

      Method:
      Surgical files of Mayo Clinic Rochester and an institutional database (1973-2015) were searched for mediastinal PGLs. Thirteen patients were previously reported (Brown ML et al, Ann Thorac Surg 2008). All cases were reviewed by a thoracic pathologist to confirm the diagnosis. Immunohistochemistry was performed using antibodies to SDHB, Ki-67, ATRX, p53, PD-L1 (clone SP263) and ASCL1. Ki-67 labelling index (LI) was calculated as the mean percent Ki-67-positive cells per 3 HPF. Next generation sequencing (NGS) used a 50-gene neuro-oncology panel. Clinical data were retrieved from medical records. Statistical analysis was performed.

      Result:
      Twenty-four patients with mediastinal PGLs (7 men, 29.2%) had a median age at time of surgery of 44.6 years (19.8-72.2). Twenty-one (87.5%) paragangliomas were completely resected, 3 had an incomplete resection. The median tumor size was 5.1 cm (1.6-14). The median Ki-67 LI was 4.1% (0.5-29.7). PD-L1 was expressed in 10% (n=2), 1% (n=4) or 0% (n=17) of tumor cells. ASCL1 was focally expressed in 2 of 23 (8.7%) cases. Diffuse loss of SDHB expression was seen in 17 of 22 (77.3%) cases. ATRX was expressed in all 22 cases tested, but its expression was patchy in 1 case that showed ATRX duplication by NGS. NGS, performed in 19 cases, revealed a single pathogenic mutation in 10 cases including SDHB (n=3), SDHD (n=6) and ATRX (n=1); and two or more mutations in 2 cases including SDHC+TERT (n=1) and SDHB+ATRX+TP53 (n=1). Two additional patients were found to have an SDHB mutation. Ten of 21 patients with available SDHx mutation status (47.6%) had no SDHx mutation. Median follow up, available in 21 patients, was 4.7 years (0.8-11.5). Five patients (2 of which with SDHx mutation) developed metastases and/or recurrence; 4 patients (2 without SDHx mutation, 2 with unknown SDHx mutation status) died (1 perisurgically, 3 of unknown cause at 2.3, 5.8, and 10.6 years after surgery each). Statistical analysis of clinicopathologic features based upon SDHx mutation could not be performed due to the small number of cases.

      Conclusion:
      Our study demonstrates that the majority of mediastinal PGLs harbors an SDHx gene mutation. Alterations in ATRX gene might represent another genetic event in mediastinal PGLs.

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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 2
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      P2.02-042 - Clinical Significance of the Tumor Expression of PD-L1 Using Four Immunohistochemistry Assays in Non-Small Cell Lung Cancer. Multicentre Study (ID 10235)

      09:30 - 16:00  |  Author(s): Anja C Roden

      • Abstract

      Background:
      PD-L1 expression level in lung cancer may be a predictive biomarker for the use of PD1/PD-L1 inhibitors. However, the reproducibility of PD-L1 staining using different antibodies and platforms is still a matter of debate. We investigated whether the PD-L1 expression in Non-small lung cancer is associated with specific clinical features or survival using four different antibodies.

      Method:
      PD-L1 status was assessed with IHC (AB clone SP142 and SP263 - Ventana, 22C3 and 28-8 - Dako) on archival FFPE surgical tumor specimens, arrayed on tissue microarrays (TMAs) with duplicate 1 mm cores from two institutions (Karolinska University Hospital and Nagasaki University Hospital). All patients (n = 682) underwent curative surgery between 1987 and 2015. The following cases were excluded from survival analysis (n = 89): R1 resection, early post-operative mortality, adjuvant chemo- or radiotherapy. PD-L1 staining was scored as positive if present in >1% of tumor cells, independently of staining intensity.

      Result:
      Patient and tumor characteristics were as follows. Median age (IQR): 68 years (27-89); gender: male/female 54%/46%; histology: squamous-cell carcinoma (SCC)/Non-squamous (N-Sq)-NSCLC/carcinoid 219 (32%)/394 (58%)/45(7%); p-stage: IA/IB/IIA/IIB/IIIA/IIIB 50%/26%/10%/10%/2%/0.2%. Median overall survival was 74 months. PD-L1 28-8 was positive in 11% of cases (SCC (56%)/N-Sq-NSCLC(40%), Pearson Chi-square p<0.0001). PD-L1 positivity (>50%) 22C3/SP263/SP142 was 10%/13%/3%. All carcinoids were negative for PD-L1. In PD-L1-SP263 positive cases, the staining intensity and distribution had a homogenous pattern between the 2 TMA cores. In NSCLC, PD-L1 positivity for each antibody was associated with tumour size (T1/T2-4; Fisher’s exact test, p<0.001) and grade of differentiation (G1, G2 and G3; p<0.0002). Statistically significant association between PD-L1 expression and OS was only observed using the clone SP263 (log-rank p=0.013).

      Conclusion:
      In this surgical series, the clone SP142 showed less PD-L1 expression in the tumour cells. PD-L1 expression was associated with tumour size, grading and only the clone SP263 showed association between its expression and survival ratio.

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      P2.02-043 - Multicentre Assessment of PD-L1 Immunohistochemistry: Challenges for Establishing the Concordance Between Four Different Antibodies (ID 10275)

      09:30 - 16:00  |  Author(s): Anja C Roden

      • Abstract

      Background:
      PD-L1 status in lung cancer may be a predictive biomarker for the use of PD1/PD-L1 inhibitors. Nonetheless, the reproducibility of PD-L1 staining using different antibodies and platforms is still a matter of debate. We investigated the performance of four different antibodies with two different platforms in two different institutions.

      Method:
      PD-L1 expression was assessed with IHC (AB clone SP142 and SP263 - Ventana, 22C3 and 28-8 - Dako) on archival FFPE surgical tumour specimens, arrayed on tissue microarrays (TMAs) with duplicated 1 mm cores from two institutions (Karolinska University Hospital and Nagasaki University Hospital). All patients (n = 682) underwent curative surgery between 1987 and 2015. PD-L1 staining was scored as positive if present in ³1% of tumor cells, independently of staining intensity. The slides were scanned and scored by seven experienced pathologists who estimated the expression of PD-L1 in the tumour and inflammatory cells. The statistical analyses were performed to compare the four different antibodies and the scoring of the pathologists on the tumour and inflammatory cells.

      Result:
      PD-L1 positivity ³1% of tumor cells using clones 28-8 / 22C3 / SP263 / SP142 was 32%/29%/33%/9%, respectively. All carcinoids were negative for PD-L1. SP142 showed a significantly lower mean score compared with other clones. PD-L1 positivity ³50% of tumour cells using clones 28-8 / 22C3 / SP263 / SP142 was 11%/10%/13%/3%, respectively. The pair comparison analysis in the tumour cells showed that the score from the highest agreement was between 28-8 and 22C3 (Kappa 0.75, CI95% 0.70-0.80) and the lowest concordance was between SP263 and SP142 (Kappa 0.21, CI95% 0.16-0.27). The evaluation of the concordance in the inflammatory cells and among the pathologists is ongoing.

      Conclusion:
      The present study shows a comparative analysis using four different antibodies. The clone SP142 shows significantly lower expression of PD-L1 in the tumour cells. The clones 28-8, 22C3 and SP263 showed an excellent concordance in the tumour cells with two different cut offs (>1% an >50%) showing a good reproducibility for the pathology assay. The highest agreement was between the clones 28-8 and 22C3. The lowest concordance was between the clones SP263 and SP142.

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    SH 03 - WCLC 2017 Highlights of the Previous Day (ID 628)

    • Event: WCLC 2017
    • Type: Scientific Highlights
    • Track: Advanced NSCLC
    • Presentations: 1
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      SH 03.03 - Biology/Pathology and Epidemiology/Primary Prevention/Tobacco Control and Cessation (ID 10931)

      07:00 - 08:00  |  Presenting Author(s): Anja C Roden

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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