title: The evaluation of E-Cadherin and vimentin as biomarkers of clinical outcomes among patients with non-small cell lung cancer treated with erlotinib as second- or third-line therapy.
abstract: E-Cadherin and vimentin protein expression was assessed in late stage non-small cell lung cancer tumors from the placebo controlled clinical trial, NCIC-CTG BR.21, to determine if these markers had the potential to predict outcome of erlotinib therapy. E-Cadherin and vimentin protein expression levels were assessed in tumors from 95 patients, who were representative of the overall population, using semi-quantitative immunohistochemistry. The percentage of tumor cells with grades 0, 1, 2, or 3 membrane staining of E-cadherin and cytoplasmic staining of vimentin was measured. Three scoring methods and multiple cut-offs were explored to determine if these markers were able to divide patients into groups with different overall survival (OS). A cut-off point for E-cadherin of ≥40% tumor cells with staining of +2 and +3 and a cut-off for vimentin of ≥10% of tumors cell with any staining provided the optimal stratification. The OS hazard ratio (HR) for E-cadherin(+) versus E-cadherin(-) in the erlotinib-treated patients was 0.68 (0.35-1.33) compared with 1.48 (0.69-3.15) in the placebo patients and the OS (HR) for erlotinib versus placebo was 0.47 (0.26-0.88) in E-cadherin(+) patients compared with 1.12 (0.52-2.44) in the E-cadherin(-) patients. The OS (HR) for vimentin(+) versus vimentin(-) in the erlotinib-treated patients was 0.65 (0.31-1.38) compared to 2.32 (1.09-4.94) in the placebo-treated patients and the OS (HR) for erlotinib versus placebo was 0.26 (0.11-0.63) in vimentin(+) compared to 0.99 (0.55-1.76) in the vimentin(-) patients. Similar trends were observed for progression-free survival and response rate. E-Cadherin and vimentin are biomarkers worthy of additional study as predictive markers of outcome of erlotinib therapy.
authors.affiliation: OSI Pharmaceuticals LLC, 2860 Wilderness Place, Boulder, CO 80301, USA. frichar214@msn.com
authors.forename: Frank
authors.initials: F
authors.lastname: Richardson
authors.forename: G David
authors.initials: GD
authors.lastname: Young
authors.forename: Regina
authors.initials: R
authors.lastname: Sennello
authors.forename: Julie
authors.initials: J
authors.lastname: Wolf
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Argast
authors.forename: Peter
authors.initials: P
authors.lastname: Mercado
authors.forename: Angela
authors.initials: A
authors.lastname: Davies
authors.forename: David M
authors.initials: DM
authors.lastname: Epstein
authors.forename: Bret
authors.initials: B
authors.lastname: Wacker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015820:Cadherins / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011799:Quinazolines / Q000627:therapeutic use*; D014746:Vimentin / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D011799:Quinazolines; D014746:Vimentin; D000069347:Erlotinib Hydrochloride