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• 12441

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  P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

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

  • 12485

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    P3.06-045 - E-Cadherin and vimentin as biomarkers of clinical outcomes among EGFR+ lung adenocarcinoma (LA) patients treated with erlotinib (CLICaP) (ID 3025)

    09:30 - 09:30  |  Author(s): D. Torres
    • Abstract

    Background
    Epithelial-mesenchymal transition (EMT) has been known to play a key role in stromal invasion of lung adenocarcinoma. Loss of E-cadherin and acquisition of vimentin are two critical steps in EMT, that are induced by Snail-1 and TWIST upregulation associated with overexpression of epidermal growth factor receptor (EGFR). However, roles of EMT-related proteins in EGFR mutants have not been fully elucidated. We investigated the inmunoexpression of EMT-related proteins in EGFR lung adenocarcinoma to demonstrate their key roles in tumor progression.

    Methods
    E-Cadherin and vimentin expression was assessed in 84 patients with EGFR+ LA to determine if these markers had the potential to predict clinical outcomes in patients treated with Erlotinib. The percentage of tumor cells with grades 0, 1, 2, or 3 membrane staining of E-Cadherin and cytoplasmic staining of vimentin was measured. We selected previously reported cut-off points shown to provide optimal stratification: ≥40% of tumor cells with staining of +2 and +3 for E.cadherin and ≥10% of tumors cell with any staining for vimentin. Overall response rates (ORR), clinical benefit (CB), time to progression (TTP), and overall survival (OS) were estimated, as well as variables that influenced OS.

    Results
    Mean age was 59.6 years (SD +/- 13.1) and 79.8% of patients were women. Mutations of EGFR, L858R and G719X in exon 19 were present in 61%, 31% and 6% respectively. Vimentin expression was strong in 9.5% (n=8) and E-cadherine expression was weak in 51.2%, moderate in 23.8% and strong in 23.8%. Highest positivity of E-Cadherin was related to exon 19 deletion (p=0-001) but not to L858R mutations (p=0.14). Strong vimentin reactivity was associated with history of smoking (p=0.03). OS was 12.3 [10-14], 27.0 [23-31],26.1 [20-32] and 33.5 [30-36] months when E-cadherine expression was negative, weak, moderate and strong (p=0.05). OS was 33 months [31-35] in vimentin-negative and 8.2 months [6-10] in vimentin-positive (p=0.001). Similar trends were observed for progression-free survival and response rate.

    Conclusion
    E-Cadherin and vimentin are valuable predictive biomarkers for EGFR+ patients. These results warrant further research on EMT in selected populations exposed to erlotinib.