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Cristian Ortiz -Villalón



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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  |  Presenting Author(s): Cristian Ortiz -Villalón

      • 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  |  Presenting Author(s): Cristian Ortiz -Villalón

      • 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.