Presence of Epidermal Growth Factor Receptor (EGFR) Mutation Predicts a Lower Grade Morphology and Lower AJCC Stage in Patients with Lung Adenocarcinoma
Celina Villa, Anjana Yeldandi, Ritu Nayar, Philip Cagle, Kirtee Raparia. Northwestern University, Chicago, IL; The Methodist Hospital, Houston, TX
Background: Epidermal growth factor receptor (EGFR) mutations predict favorable response to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer but the histopathologic features associated with this mutation have not been well described. We performed this study to determine the relationship between EGFR mutations, clinicopathologic features and tumor stage according to current American Joint Committee on Cancer (AJCC) staging.
Design: EGFR mutation in exons 18, 19, 20 and 21 were screened in 281 patients with lung adenocarcinoma diagnosed between 2008 and 2011 using PCR and Qiagen pyromark 24 sequencer. Histopathologic characteristics were reviewed and correlated with mutation status using appropriate parametric and non-parametric tests for significance.
Results: EGFR mutations occurred in 20% (57/281) of all lung carcinomas. The EGFR mutant group had a male to female ratio of 1:3.4 and mean age of 67 years (range 39 to 90). Mutations seen were L858R, exon 21 (n=18); E746, exon 19 (n=16); L747, exon 19 (n=9); exon 19 deletions (n=4); G719A, exon 19 (n=3); S7681, exon 20 (n=2); L861Q, exon 21(n=2); T790M, exon 20 (n=1); P848L, exon 21 (n=1) and E709, exon 18 (n=1). EGFR mutant patients were more likely to have lower grade morphology, compared to patients with wild type gene.
Grade 1 morphology was seen in 35% of EGFR mutants, compared to 13% of wild types (p<0.0001). Minimally invasive adenocarcinoma was seen in 12% of EGFR mutants, compared to 6% of wild-types. The predominant pattern seen in EGFR mutants were acinar (42%) and lepidic (37%), compared to wild types (acinar in 62% and lepidic in 10%, p<0.0001). 50% of EGFR mutants had N0 nodal status and 7% had pleural invasion. 61% of EGFR mutants had Stage 1 disease, compared to 39% in wild types (p= 0.001).
Conclusions: L858R in exon 21 and E746 in exon 19 mutations were the most frequent mutations. Patients with EGFR mutation were similar to patients with wild type EGFR with respect to age, sex, tumor size, minimally invasive adenocarcinoma, nodal status and pleural invasion. The presence of EGFR mutation predicts lower grade morphology and a lower AJCC stage in patients with adenocarcinoma of lung.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 289, Monday Morning