Abstract
e19117 Background: An epithelial phenotype in NSCLC is associated with improved sensitivity to EGFR tyrosine kinase inhibitors (TKI). The best method to identify this subset is unknown (Richardson Anticancer Research 2012, Byers Clin Cancer Res 2012). This retrospective study correlates E-cadherin (Ecad) and vimentin (vim) immunohistochemistry (IHC) expression with outcomes in advanced NSCLC patients (pts) treated with erlotinib (E). Methods: Advanced NSCLC pts that received E were included if sufficient tumor was available from diagnosis. IHC scores for E-cad and vim were generated by multiplying frequency (0-4) by intensity (0-4). Log Rank was used to correlate IHC expression with progression free and overall survival (PFS, OS). Results were compared to a subset of pts with tissue from primary surgical NSCLC resection who later received E for recurrent disease. Results: 159 advanced NSCLC pts treated with E had tissue from diagnosis and IHC analysis. There was no correlation with PFS or OS on E and high/low vim or Ecad expression. Subtracting the IHC scores (vim minus ecad) created a difference score. A low difference score (n = 62) correlated with prolonged PFS (2.6 vs 1.9 months, p = .014 HR 1.52) compared with a high score, n = 97. Low difference score trended toward prolonged OS (p=.46) 33 of the patients had tissue available from primary surgical resection. The invasive front was examined for membranous E-cad and cytoplasmic vim (Allred score 0-8). Patients with low vim (< 4) and Ecad (>5), n= 19, trended toward prolonged PFS and OS on E compared with patients with high vim (>5) and low Ecad (<6), n=10 (4.2 vs 1.6 months and 15.5 vs 6.5 months, respectively, p=NS). Conclusions: In this retrospective analysis, using unselected, frequently small tissue specimens, the expression of ecad or vim alone by IHC did not correlate with outcomes for E treated patients. A complicated difference score (vimentin score minus ecadherin score) did correlate with PFS on E. Examining EMT markers at the invasive edge of resected NSCLC tumors might more accurately assess EMT activity and its relationship to outcomes when these pts are recommended EGFR-TKIs.
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