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R. Lewensohn



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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-074 - Exosomal RNA-Profiling of Lung Pleural Effusions Identifies Adenocarcinoma Patients through Elevated miR-200 Expression (ID 8919)

      09:30 - 09:30  |  Author(s): R. Lewensohn

      • Abstract
      • Slides

      Background:
      The inherent challenges associated with lung tissue biopsies have spurred an enormous interest in the use of liquid biopsies. Pleural effusions are one such liquid biopsy which may enable lung cancer profiling and also assess if the patient suffers from a benign or malignant process in the lungs. Recently extracellular vesicles of endocytic origin, exosomes, have attracted interest as liquid biopsy of tumors since they can be used to look at tumor derived mutations as well as tumor cell activity represented by the RNA transcriptome. The RNA cargo carried in exosomes is known to resemble the RNA profile of the primary tumor. Here we aimed to analyze if microRNA and targeted cancer mRNA profiling of exosomes isolated from pleural effusions could decipher biomarkers associated with lung adenocarcinoma.

      Method:
      A systematic microRNA profiling of matured processed microRNAs along with targeted cancer mRNA profiling was carried out on extracellular vesicles, including exosomes, derived from 36 clinical pleural effusions, separated into 18 benign and 18 lung adenocarcinoma samples. Benign pleural effusion consisted of unspecific inflammation in the majority of cases. The two groups were well balanced with respect to age (median = 72Y) and smoking history (ever smokers in circa 70% of cases). However, males were overrepresented in the benign group (83% vs 44%). Both microRNA and mRNA profiling was conducted using TaqMan RT-qPCR Open Arrays (containing 800 genes each) followed by statistical ranking (Wilcoxon test) of differentially regulated transcripts between the two patient groups.

      Result:
      Systematic RNA profiling revealed a substantial, and highly significant (p<0.0001), elevated expression of all members from the extended miR-200 family in pleural effusions collected from patients with NSCLC adenocarcinoma. By cross-analyzing the obtained microRNA profiling data to the mRNA cancer panel expression, statistical enrichment between miR-200 family members and predicted miR-200 target genes, including PIK3CA, NOTCH1 and KRAS was observed (Fisher’s exact test, p=0.0105).

      Conclusion:
      Our study demonstrates the usage of exosomal RNA profiling from pleural effusions to define patients with lung adenocarcinoma and further highlights miR-200 microRNAs as diagnostic markers in lung cancer liquid biopsies. Acknowledgment: This study was supported from the following funding bodies: Swedish Cancer Society, Stockholm Cancer Society, Stockholm County Council, Knut and Alice Wallenberg Foundation and Erling Persson Family Foundation.

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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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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 - 09:30  |  Author(s): R. Lewensohn

      • 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.