Abstract
Introduction: Approximately 70% of lung adenocarcinomas express TTF-1. EGFR mutations are present in 13-15% of Western adenocarcinoma patients. This paper investigates TTF1 as a negative predictor of mutant EGFR in lung adenocarcinomas. Results: In the pilot cohort (N = 301) two of 224 specimens positive for EGFR mutations had negative TTF-1 expression (sensitivity 99.1%, 95% confidence interval (CI) 96.8-99.9%). Estimated negative predictive values (NPV) for EGFR mutation prevalence rates of 13% and 15% are 99.5% (95% credible interval (CRI) 98.6%- 99.9%) and 99.4% (CRI - 98.4%-99.9%). For EGFR mutation rates of 13% and 15%, using validation cohort data (211 patients), the estimated NPVs were 97% (95% CRI 92%-99%) and 96% (95% CRI 91%-99%). Methods: Formalin-fixed paraffin-embedded tumors from lung adenocarcinoma patients were analyzed for EGFR mutations by allele-specific PCR in the 'pilot cohort'. TTF-1 status was documented as positive or negative. Negative predictive value (NPV) for a range of true prevalence of EGFR mutation (1%-50%) was estimated using Bayesian modeling. The hypothesis was validated in a separate 'validation' cohort using the same modeling. Conclusion: An overwhelming majority of TTF-1 negative adenocarcinomas will be negative for EGFR mutations. This finding allows for earlier initiation of chemotherapy in newly diagnosed TTF-1 negative adenocarcinomas of the lung with stage IV disease.
Original language | English (US) |
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Pages (from-to) | 522-528 |
Number of pages | 7 |
Journal | Oncoscience |
Volume | 1 |
Issue number | 8 |
DOIs | |
State | Published - 2014 |
Keywords
- Adenocarcinoma
- EGFR
- NSCLC
- TTF-1
ASJC Scopus subject areas
- Oncology
- Cancer Research