Epidermal growth factor receptor (EGFR) mutations are exceptionally rare in thyroid transcription factor (TTF-1)-negative adenocarcinomas of the lung

• Published in: Oncoscience 2014-08, Vol.1 (8), p.522-528
• Main Authors: Somaiah, Neeta, Fidler, Mary Jo, Garrett-Mayer, Elizabeth, Wahlquist, Amy, Shirai, Keisuke, Buckingham, Lela, Hensing, Thomas, Bonomi, Philip, Simon, George R
• Format: Article
• Language: English
• Subjects: Clinical Report
• ISSN: 2331-4737; 2331-4737
• DOI: 10.18632/oncoscience.72

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. 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%). 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. 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.