Abstract 3403: E-cadherin and vimentin patterns by immunohistochemistry identify epithelial and mesenchymal phenotypes in lung adenocarcinoma

Abstract

Abstract Purpose: To examine markers of epithelial-mesenchymal transition (EMT) in lung adenocarcinoma (ADC) defining epithelial-like (EPT) and mesenchymal-like (MES) phenotypes and correlate these with outcomes, in addition to other EMT markers. This study examined 33 patients with lung adenocarcinoma (ADC) who underwent surgical resection and later at disease progression received erlotinib. Experimental Design: All slides with tumor from resection specimens were reviewed (mean 4.8/case; range 1-9). Tumors were histologically subtyped according to recent IASLC classification. Tumor budding was graded per Ueno et al. (2002). A block containing the invasive front was selected for IHC staining with antibodies to e-cadherin (ECAD), vimentin (VIM), β-catenin (α-CAT), and SNAI1. Pattern-specific staining was evaluated at the invasive tumor front: E-cadherin-membranous, vimentin-cytoplasmic, α-CAT-membranous, SNAI1-nuclear, cytoplasmic. Complete circumferential membranous staining for e-cadherin was scored as present/absent; other markers were scored by the Allred system (0-8). PFS and OS were calculated from time of diagnosis to disease progression or death. Results: Two distinct phenotypes were identified with ECAD and VIM: EPT showing preserved membrane ECAD staining with low VIM (≥4) (N=19) and MES showing weak/absent membrane ECAD staining with high VIM (Δ5) (N=10). Median PFS for EPT group was 4.2 mo vs MES 1.6 mo; median OS for EPT group 15.5 mo vs 6.5 mo. These differences were not statistically significant. No association was found between high grade tumor budding and EPT vs MES phenotype p=0.221). Membranous α-CAT expression and nuclear SNAI1 expression showed a statistically significant correlation with EPT vs MES (β-catenin mean score 7.8 vs 6.1, p=0.0184) and (nuclear SNAI1 mean score 7.3 vs 6.1, p=0.0364). Conclusions: Epithelial and mesenchymal phenotypes can be identified by IHC for e-cadherin and vimentin. These phenotypes correlate with other EMT markers β-catenin and SNAI1 but not with tumor budding. Although differences in median PFS and OS were seen between the two groups, the number of cases is too small to identify a statistically significant difference. The results do support the rationale for defining EPT and MES groups for prognosis in a larger group of early-stage surgically resected patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3403. doi:1538-7445.AM2012-3403