Author of

• 10923

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  P1.18 - Poster Session 1 - Pathology (ID 175)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10935

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    P1.18-012 - Thyroid transcription factor (TTF-1) negative lung adenocarcinomas will be wild type for epidermal growth factor receptor (EGFR) mutations. (ID 2036)

    09:30 - 09:30  |  Author(s): T. Hensing
    • Abstract

    Background
    TTF-1 is expressed in approximately 70% of adenocarcinomas (ACs) of the lung. EGFR mutations are present in 13-15% of unselected patients with AC in the United States and national guidelines suggest initiating first line EGFR tyrosine kinase inhibitors in this population. Both high TTF1 expression and EGFR mutations are associated with terminal respiratory unit (TRU) type ACs, female sex, never-smoking status and longer survival. We hypothesized that TTF-1 negative AC would have a high probability of being negative for EGFR mutations.

    Methods
    Microdissected formalin-fixed paraffin-embedded tumors from 693 patients with NSCLC were analyzed for EGFR mutations by allele-specific PCR in a pilot data set to test the hypothesis (pilot cohort). TTF-1 status was documented as positive, negative or not reported. Negative predictive value (NPV) for a range of true prevalences of EGFR mutation (1%-50%) was estimated using a Bayesian modeling approach. To further corroborate the hypothesis, a separate validation cohort of patients treated with erlotinib at two academic affiliated institutions with known TTF1 and EGFR mutation status was studied using the same modeling approach (validation cohort).

    Results
    301 patients with documented ACs and known TTF-1 status were included in the pilot cohort. In this population enriched to have EGFR mutations, EGFR mutations were present in 224 specimens (74%). Only 2 of the 224 specimens that were positive for EGFR mutations were negative for TTF-1 expression yielding a sensitivity of 99.1% (95% confidence interval (CI) 96.8-99.9%). For prevalence rates of EGFR mutations of 13% and 15%, the estimated NPV are 99.5% (95% credible interval (CRI) 98.6%-99.9%) and 99.4% (98.4%-99.9%), respectively. Data from 211 patients comprised the validation cohort. With an 11% rate of EGFR mutations, the estimated NPV was 92% (95% CRI - 73%-99%). For true EGFR mutation rates of 13% and 15%, using the data from the validation cohort, the estimated NPVs were 97% (95% CRI 92%-99%) and 96% (95% CRI 91%-99%), respectively. Figure 1. estimated NPVby true prevalence of EGFR mutation for both datasets Figure 1

    Conclusion
    An overwhelming majority of Lung ACs that are TTF-1 negative will be negative for EGFR mutations. These findings may be useful in avoiding delay of chemotherapy initiation in TTF-1 negative patients with newly diagnosed non-small cell lung cancer.