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S.Y. Park



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    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P3.02-016 - Correlation of Programmed Cell Death Ligand-1 Messenger RNA and Protein Expression in Non-Small Cell Lung Cancer    (ID 9472)

      09:30 - 09:30  |  Author(s): S.Y. Park

      • Abstract
      • Slides

      Background:
      Monoclonal antibodies targeting the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have been showing promising results in advanced non-small cell lung cancer (NSCLC). Here, we investigated PD-L1 messenger RNA (mRNA) expression by a novel RNA in situ hybridization technique and compared it with PD-L1 protein expression in NSCLC.

      Method:
      Primary NSCLC specimens of 687 patients (476 adenocarcinoma and 211 squamous cell carcinoma) were constructed into tissue microarrays. PD-L1 mRNA in situ hybridization was performed with RNAscope[®] assay and classified using two independent scoring systems (RNA scope score and RNA proportion score). We also performed immunohistochmisty (IHC) using the Dako 22C3 pharmDx assay for evaluating PD-L1 protein expression.

      Result:
      PD-L1 mRNA expression was detected in 11.9% by RNA scope score and 8.3% by RNA proportion score. PD-L1 protein expression showed a positivity of 25.2% for the 1% cut-off, and 9.9% for the 50% cut-off. The two RNA scoring systems showed a linear correlation to each other (r = 0.83, p < 0.01), as well as to PD-L1 IHC repectively (p < 0.0001). The cut-off value that best correlated with PD-L1 protein expression was “1” for both RNA scope score (κ = 0.43 for the 1% and 0.58 for the 50% IHC cut-off) and RNA proportion score(κ = 0.36 for the 1% and 0.60 for the 50% IHC cut-off). Applying this criteria, discordant cases were found in 20% and 9% with 1% and 50% IHC cut-offs, respectively.

      Conclusion:
      PD-L1 mRNA expression, evaluated either as RNA scope score or as RNA proportion score, showed promising statistical results in predicting PD-L1 protein levels. We could thereby set out the RNA scoring system for PD-L1 in NSCLC. Discordant cases with positive mRNA levels and negative immunohistochemical results may indicate that PD-L1 mRNA in situ hybridization could be a more sensitive marker than immunohistochemistry. To verify the predictive role of PD-L1 mRNA expression in immunotherapy, however, therapeutic response to anti-PD-1/PD-L1 inhibitors should be investigated in future studies.

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