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Alejandro Aviles-Salas



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    EP1.12 - Small Cell Lung Cancer/NET (ID 202)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.12-16 - CD47 Expression and Prognosis in Patients with Small Cell Lung CancerCD47 Expression and Prognosis in Patients with Small Cell Lung Cancer (ID 2935)

      08:00 - 18:00  |  Author(s): Alejandro Aviles-Salas

      • Abstract

      Background

      CD47 is an integral membrane protein expressed in all cells. CD47 present two opposing roles in cell survival. CD47 can interact with signal-regulatory protein-α (SIRP-a) on macrophages, prevents phagocytic clearance. Besides, CD47 signaling through the thrombospondin-1 limits self-renewal and suppresses expression of the stem cell transcription factors cMyc, Sox2, Oct4, and Klf4 in non-transformed cells. Data on the clinical significance of CD47 expression in patients with small cell lung cancer remain limited.

      Method

      Forty-five naive patients with small cell lung cancer diagnosis were evaluated. Tumor samples obtained by biopsy or surgical resection, were collected for CD47 evaluation. Tumor samples were scored according to the fraction of stained cells at each intensity. The staining intensity of the cell membrane was scored within a scale ranging from 0-3. To determine the prognostic and predictive biomarkers of CD47, patients were stratified according to a cutoff point. This cutoff was optimized as a function of overall survival (OS) using the X-tile and Cutoff Finder software

      Result

      Preliminary results showed that CD47 was present in 26.7% of population. We stratified the CD47 in two cohorts: CD47 positive-negative and a score of CD47>80. The CD47>80 was present mainly in patient with more than 60 years old (35% vs. 8.0%, p=0.024). Longer overall survival was associated with ECOG-PS 0-1 (20.2 vs. 6.9 p=0.001), disease stage IIIB (49.4 vs. 8.0, p=0.020), absent of CNS metastases (14.1-6.8, p=0.016) and absent of pleural effusion (16.2 vs. 6.99, p=0.002). Interestingly, patient with CD47 positive present better OS (10.8 vs. 6.99, p=0.485) but not reaching significance and patient with a score of CD47>80 have better OS (14.0 vs 9.2, p=0.296).

      Conclusion

      Immune checkpoint CD47 expressed on the surface of tumor cells allows them to escape immunosurveillance. We previously reported that high CD47 expression was associated with the presence of somatic EGFR mutations in patients with NSCLC. In these patients, high CD47 expression was an independent prognostic factor of worse progression-free survival. Recent studies have indicated that the signal-regulatory protein (SIRP)α–CD47 pathway regulate a phagocytosis checkpoint in macrophages and other innate immune cells. In contrast, in this report we found that high CD47 expression was associated with <60 years old patient and better overall survival. Previously, studies in small cells lug cancer express high levels of CD47 and the blocking of CD47 enhances phagocytosis inhibits tumor growth. CD47 have a dual role, when interact with SIRPα avoid clearance of cells, but it interacts with thrombospondin 1 inhibits cell cycle progression and induces senescence in endothelial cells. Previous studies have shown that the protein TSP1 is as potent inhibitor of angiogenesis and its antiangiogenic activity is mediated by its receptors, CD36 and CD47. In conclusion CD47 have different function according to the ligand, and is a potential biomarker in cancer

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    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.09-28 - Prognostic Impact of LKB1 Expression in Advanced Non-Small-Cell Lung Cancer (Now Available) (ID 1528)

      10:15 - 18:15  |  Author(s): Alejandro Aviles-Salas

      • Abstract
      • Slides

      Background

      LKB1 is a tumor suppressor gene that regulates cell energy homeostasis, cell polarization, and apoptosis. Within lung cancer, LKB1 ranks as the third most common mutation found in lung adenocarcinoma, both alleles are somatically inactivated in 30%. LKB1 mutations are linked to smoking history, moreover, it have been associated with more aggressive clinical phenotype in KRAS-mutant NSCLC patients, according to preclinical models. Additionally, LKB1 has been associated with primary resistance to PD-1 axis inhibitors in lung adenocarcinoma. However, its expression and clinical implication has not been extensively studied. The aim of the study was to evaluate LKB1 expression in patients with advanced NSCLC.

      Method

      In retrospective way patients with advanced NSCLC with and without EGFR mutations from México and Colombia were analyzed. Patients received therapy according EGFR status (TKI anti-EGFR or chemotherapy). Inclusion criteria were a histopathological confirmed diagnosis, adequate tissue to determine the expression of LKB1 by immunohistochemistry through the clone HPA017254 (Sigma®). The primary outcome was overall survival (OS).

      Result

      A total of 87 patients were included in the analysis, 25.3% of them had LKB1 positive expression. Median score intensity was 20%. There was a significant association of LKB1 positive expression with wood-smoke exposure (76.9 vs 23.1%, p=<0.001), EGFR mutation (54.5 vs 45.5%, p=<0.001) compared to LKB1 negative. Global Median OS was 29.7 months. Median OS for LKB1 positive was 33.3 months (CI 95%, 8.9 - 57.6) and 29.5 months (CI 95%, 26.1 - 32-8) for LKB1 negative (p=0.42). After stratifying patients by percentage of LKB1 expression, cut-off of 20% showed a tendency to increase OS in patients with ≥20% expression (figure 1); 49.9 months (IC 95%, 10.6 - 85.2 months) vs 29.5 months (IC 95%, 26.3 - 32.7 months), (p=0.068). Furthermore, a similar trend in OS was observed in patients with ≥50% expression, median OS was not reached compared with 29.5 months (IC 95%, 26.2 - 32.7 months) in patients with <50% expression (p=0.091).

      diaz garcia - figure 1.png

      Conclusion

      We found a trend to higher OS in patients with LKB1 expression >20%. This data should be confirmed in prospective study in order to determine the role of LKB1 as biomarker in NSCLC patients.

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