Absence of TTF-1 Immunoreactivity Can Predict EGFR Wild-Type in Non-Small Cell Lung Cancer (NSCLC)
Ian Bosdet, Sean S Young, Rola H Ali, B Kelly McNeil, Carrie Wong, Kristy Garbutt, Aly Karsan, Diana N Ionescu. BC Cancer Agency, Vancouver, BC, Canada
Background: Activating mutations in the epithelial growth factor receptor (EGFR) are strong predictors of efficacy for tyrosine kinase inhibitors. In-frame deletions in exon 19 and the c.2573T>G(L858R) single-base change in exon 21 together comprise over 90% of these mutations. Thyroid transcription factor 1 (TTF-1) is a tissue-specific transcription factor expressed in epithelial tissues of the lung and thyroid. TTF-1 is an important immunohistochemical marker for diagnosis of pulmonary adenocarcinoma and recent studies also suggest TTF-1 expression is a prognostic factor for increased survival in lung adenocarcinoma.
Design: EGFR tyrosine kinase inhibitor gefitinib is approved in Canada as a first line therapy for patients with stage IIIB/IV non-squamous NSCLC. Since March 2010, 548 patients in British Columbia have been tested for EGFR mutations. Tumour tissue was macrodissected from formalin-fixed, paraffin-embedded cytological samples, biopsies and resections and EGFR mutations in exons 19 and 21 were detected from the purified DNA using PCR fragment size analysis.
Results: EGFR mutations were detected in 109 of 509 samples (21.4%), 70 (13.7%) in exon 19 and 39 (7.7%) in exon 21. Of 323 samples for which TTF-1 immunohistochemistry results were available, 248 (76.8%) were TTF-1 positive and 75 (23.2%) were TTF-1 negative. There were both EGFR mutation status and TTF-1 immunohistochemistry results for 306 samples. TTF-1 expression was detected in 58 of 62 mutation-positive samples; however 178 of 244 TTF-1 positive samples were EGFR wild type. These results demonstrate that TTF-1 IHC is 93.5% sensitive and 27.1% specific for predicting the presence of EGFR activating mutations.
Conclusions: Although TTF-1 immunoreactivity is not specific for the presence of activating EGFR mutations in NSCLC, its absence can reliably predict EGFR wild type with 93.5% sensitivity. Thus, tumour TTF-1 status may be informative in the selection of patients for EGFR mutation testing.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 298, Tuesday Afternoon