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  MA09 - Lung Cancer Surgical and Molecular Pathology (ID 908)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 15:15 - 16:45, Room 202 BD

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    MA09.11 - Genomic Landscape and its Correlation with TMB, CD8 TILs and PD-L1 Expression in Chinese Lung Squamous Cell Carcinoma (ID 12370)

    16:25 - 16:30  |  Author(s): Henghui Zhang
    • Abstract
    • Presentation
    • Slides

    Background
    

    The current study aimed to comprehensively depict the genomic landscape of Chinese lung squamous cell carcinoma (LSCC) and investigate its correlation with tumor mutation burden (TMB), CD8 tumor infiltrating lymphocytes (TILs) density and PD-L1 expression.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Whole-exome sequencing (WES) were performed on tumor tissue collected from 189 patients with surgically resected LSCC. TMB was defined as total number of nonsynonymous single nucleotide and indel variants. High TMB was defined as greater than 75^th percentile. CD8+ TILs and PD-L1 expression were assessed by immunohistochemistry. We determined the 5% of CD8+ TIL or PD-L1 expression as the cut-off point for high/low CD8+ TIL or PD-L1 positive/negative expression.

    4c3880bb027f159e801041b1021e88e8 Result
    

    We found recurrent mutations (>5%) in 8 genes, including TP53, KMT2C, NFE2L2, KEAP1, CDKN2A, PTEN and FBXW7. FGFR1 and PIK3CA amplifications were found in 19% and 11% of samples. 24.9% of patients had high TMB. Except for expected differences by smoking status, baseline clinical variables were similar between those with high and low TMB. Interestingly, FGFR1, PIK3CA or SOX2 amplification was independently associated with higher TMB (P=0.020, P=0.017, P=0.029; respectively). Patients with copy number variations had significantly higher TMB than those without (P=0.009). Positive PD-L1 and CD8+ TILs expression were identified in 24.3% and 78.8% of all cases. Baseline features were comparable between those with positive and negative CD8+ TIL or PD-L1 expression. NFE2L2 mutation and PIK3CA amplification were independently associated with significantly higher PD-L1 expression (P=0.003, P=0.014; respectively). TP53 mutations were associated with higher CD8+ TILs expression (P=0.008), but FGFR1 amplification was correlated with lower CD8+ TILs expression (P=0.042). Of note, there is no association between TMB and PD-L1 expression (r=0.052, P=0.476), or CD8+ TILs expression (r=0.026, P=0.718). None of TMB, PD-L1 and CD8+ TIL expression could individually predict overall survival (OS). However, combination of TMB and PD-L1 could stratify total populations into two groups with distinct prognosis. Patients with negative PD-L1 expression and high TMB had the worst prognosis (P=0.008). Additionally, combination of TMB and CD8+ TIL expression could also divide total populations into two groups with different prognosis (worst prognosis in negative CD8+ TIL expression and high TMB, P=0.022).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    This was the first and most large-scale study to comprehensively portray genomic landscape of Chinese LSCC. The current study provides several meaningful and referential findings for the future design of clinical trials in LSCC, especially immunotherapy based on immune checkpoint inhibitors.

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