Author of

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  P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12393

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    P3.02-007 - Preferential Expression of MET in Lung Adenocarcinoma vs Lung Squamous-Cell Carcinoma (ID 1186)

    09:30 - 09:30  |  Author(s): R. Yauch
    • Abstract

    Background
    MET is a tyrosine kinase receptor expressed on the cell surface of numerous cell types, including normal and malignant epithelial cells. MET is expressed on a proportion of non-small cell lung cancer (NSCLC) cases of adenocarcinoma and squamous-cell differentiation. In a phase II clinical trial evaluating the anti-MET monovalent antibody onartuzumab, patients with advanced MET-positive NSCLC – as determined by immunohistochemistry (IHC) – derived clinical benefit from onartuzumab and erlotinib. The prevalence of MET expression in two separate sample cohorts of NSCLC – vendor-procured and phase II clinical trial samples – is compared and correlated with MET gene copy number.

    Methods
    Formalin-fixed, paraffin-embedded NSCLC tissues were obtained from commercial sources or from the phase II clinical trial OAM4558g. Tumor histology was determined by morphology; IHC for TTF1 and p63, respectively; or both. MET IHC was performed with the SP44 rabbit monoclonal antibody (CONFIRM anti-Total c-MET) on a Ventana Benchmark XT platform. Patients were selected based on expression of MET by IHC as defined by moderate or strong staining in at least 50% of tumor cells (clinical score 2+/3+); MET gene copy number was determined by fluorescence in-situ hybridization (FISH) or by chromogenic in-situ hybridization (CISH) (INFORM® MET DNA probe, Ventana Medical Systems).

    Results
    Adenocarcinomas and squamous-cell carcinomas accounted for 46% (n=95) and 54% (n=110) of the vendor-procured samples and for 59% (n=75) and 28% (n=36) of clinical trial samples, respectively. In total, 16% (n=33) of vendor-procured and 52% of clinical trial samples were scored as MET-positive. The proportions of MET-positive cases among adenocarcinomas and squamous-cell carcinomas were 24% and 9% for vendor samples and 61% and 28% for clinical trial samples. FISH analysis of the OAM4558g clinical trial samples showed MET gene amplification in 8 of 96 cases (8%) with a high positive correlation to MET-positive IHC status; 6 of 8 gene-amplified cases were MET-positive by IHC (p<0.0001). Evaluation of MET copy number by CISH is ongoing and will be reported.

    Sample Source	Clinical Trial OAM4558g		Vendor-Procured
    Histology	Adenocarcinoma	Squamous-cell Carcinoma	Adenocarcinoma	Squamous-cell Carcinoma
    Cases (n)	75	36	95	110
    MET-positive (%)	61	28	24	9

    Conclusion
    These results demonstrate preferential MET expression for adenocarcinoma compared with the squamous-cell carcinoma subtype of NSCLC. The lower proportion of MET-positive cases in the vendor samples suggests that tissue quality is crucial for adequate MET assessment by IHC.