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Toyin Adefila-Ideozu



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    Mini Oral session II (ID 63)

    • Event: ELCC 2019
    • Type: Mini Oral session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 16:40 - 17:40, Room C
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      1O - Impact of MET variants on PD-L1 expression in pleomorphic lung carcinoma (ID 495)

      16:40 - 17:40  |  Author(s): Toyin Adefila-Ideozu

      • Abstract
      • Presentation
      • Slides

      Background

      Pleomorphic Lung Carcinoma (PC) is a rare subtype of NSCLCs poorly responsive to systemic therapy. It is a heterogenous tumour with both epithelial and sarcomatoid components. MET variants are targetable aberrations and have recently been reported to be more frequent in PCs. The relationship between MET and PD-L1 expression is not well understood. We determined PD-L1 expression in PCs and its relationship with MET variants.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      80 cases of pleomorphic carcinoma were identified from the biobank and diagnostic archives of Royal Brompton Hospital and Imperial College Healthcare NHS trust. DNA was isolated for determination of a. MET copy number by digital droplet PCR (ddPCR) and b. Genomic MET aberrations by NGS. IHC of PD-L1 (28-8) with % positive cells were scored by two pathologists independently and >49% tumour staining was defined as high.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      78 cases were evaluated for PD-L1 status with a median score of 44%. 23/63 (36%) cases had MET CN of > 2.2. METex14 splice variants were identified in 5/73 (7.2%) cases. 2/73 (2.7%) cases had deleterious MET mutations. By MET CN status: low/normal MET CN (<2.3) median PDL1 expression was higher (50%) than in high MET CN ( > =2.3: 37.5%; P = 0.18). This translates into a significantly fewer number of high PD-L1 expressors (>49%) in cases with high MET CN (>2.2; P = 0.06; Table). There was no significant difference in PDL1 expression between MET mutation vs. wild-type (P = 0.9)

      MET copy number and PDL-1 expression

      PD-L1 ExpressionMET CN < 2.3MET CN > =2.3Total
      PD-L1<50%20 (50%)17 (74%)37
      PD-L1 >50%20 (50%)6 (26%)26
      .

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      PCs have high levels of PD-L1 expression. There is an inverse relationship between MET CN and PD-L1 expression. This has implications when using checkpoint inhibitors for cases with MET copy number gain in NSCLC. Further evaluation is needed to better understand response to checkpoint inhibitors of PC cases with MET CN gain.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The Royal Marsden Foundation NHS Trust.

      213f68309caaa4ccc14d5f99789640ad Funding

      National Institute for Health Research (NIHR) and British Lung Foundation.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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