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Anne Bowcock

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    MA21 - Molecular Subtyping, CBL3, and Non Coding RNA (ID 924)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 205 BD
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      MA21.03 - Heterogeneity in MET Copy Number and Intratumoural Subsets in Pleomorphic Lung Carcinoma: Implications for MET Directed Therapy in NSCLC (ID 13061)

      15:25 - 15:30  |  Author(s): Anne Bowcock

      • Abstract
      • Presentation
      • Slides


      Pleomorphic Lung Carcinoma (PC) is a rare subtype of NSCLC poorly responsive to systemic therapy. Both epithelial and sarcomatoid phenotypes exist, suggesting an important role of epithelial-to-mesenchymal transition. We aimed to determine MET copy number (CN) within individual tumour components and establish its correlation with immunohistochemistry (IHC) expression.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Histopathological assessment and diagnosis was confirmed for 57 cases of resected PCs from the Royal Brompton Hospital Biobank. DNA was isolated from multiple regions and MET copy number determined by digital droplet PCR (ddPCR). IHC using c-MET (EP1454Y) and H-scores were assigned independently by two histopathologists.

      4c3880bb027f159e801041b1021e88e8 Result

      Cases: median age 66 years, 36.2% T3, 41.4% T2 and 13.8% T1. In the epithelial areas, adenocarcinoma was the most common (45.6%) followed by undifferentiated NSCLC (22.8%) and squamous (17.5%): in pleomorphic areas, mixed giant/spindle cell (35%), spindle cell (31%) and giant cell (26%). MET-CN gain by ddPCR was seen in 25/58 (44%) of cases (CN>2.3). 3/58 (5%) had CN>5. There was a significantly higher MET-CN in pleomorphic compared to epithelial areas (2.7 versus 2.2 P = 0.046). While this did not correlate with c-MET IHC, an H-score of >223 had 75% sensitivity and 52.4% specificity for MET-CN >5.0 (Figure).

      met expression in pc2.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is intra-tumoral heterogeneity in MET-CN between tumoural subsets. This may account for the development of pleomorphic phenotypes in PC. Consequently MET-directed therapies such as crizotinib may be highly effective only against the MET-amplified component in PC and may not impact on overall tumoural control due to minimal efficacy in the non-amplified epithelial component. MET expression using IHC does not correlate with MET-CN determined by ddPCR, although may provide a screening tool for MET amplification. MET aberrations are potentially druggable and therefore this has implications for sampling and MET testing.


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