Author of

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  P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 26800

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    P2.01-06 - HSP72 Expression Associates with Survival in EGFR Mutated NSCLC (ID 14285)

    16:45 - 18:00  |  Author(s): Paul Frankel
    • Abstract

    Background
    

    Heat shock protein 72 (HSP72) was observed to be important for editing DNA replication errors and repairing base damage. EGFR mediates HSP72 Y41 stability via phosphorylation. EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy inhibited phosphorylation of HSP72 leads to its degradation with suppression of polymerase α (Polα) and a resultant increase in overall mutation rate in EGFR mutant lung cancer cells. Our primary objective was to determine if baseline HSP72 expression is a prognostic biomarker for NSCLC patients with EGFR mutant NSCLC.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    A retrospective cohort of patients was identified with known EGFR mutation positive NSCLC and available tissue from the City of Hope Comprehensive Cancer Center seen between 2008 and 2016. Immunohistochemical (IHC) analysis was performed to analyze HSP72 levels. A chi-square test for categorical data and multivariate logistic regression analyses was used to study the relation between HSP72 expression and the other clinical and demographic data.

    4c3880bb027f159e801041b1021e88e8 Result
    

    48 patients with EGFR mutated NSCLC and available tissue were identified. The median age was 64 range (39-84) with 50% Asian (n = 24), Caucasian 38% (n = 18), and African American 8% (n = 4) and other 4% (n = 2). Most patients were Stage IV at initial diagnosis (n = 41, 85%), other were Stage IB (n = 2), Stage IIB (n = 1), Stage IIIA (n = 1) and Stage IIIB (n = 3). HSP72 expression was 0 in 16 patients, 1 in 15 patients, 2 in 9 patients and 3 in 8 patients. Median survival of HSP72 0, 1, 2,3 were 28.3, 42.4, 41.2, and 107.7 months respectively (p < 0.02, log-rank test). In univariate Cox regression analysis, HSP72 expression of 3 compared to others correlated with an HR of 0.23 (95% CI 0.07-0.77). When stratifying by stage (Stage IV vs all others), the HR associated with an HSP72 expression of 3 was 0.22 (95% CI 0.05-0.97), and the signal for HSP72 was also significant when stratifying by stage and considering HSP72 score as either a continuous marker or as the four categories (0,1,2,3). There was no relationship noted in the change in HSP72 values as tumors transformed from T790M- to T790M+, and no relationship related to L858R or exon 19 deletions.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    In EGFR mutated NSCLC, high levels of HSP72 expression are associated with improved survival. Further investigations are evaluating mechanisms of increased DNA damage following EGFR TKI therapy and association with the development of resistance.

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