title: Assessment of folate receptor-α and epidermal growth factor receptor expression in pemetrexed-treated non-small-cell lung cancer patients.
abstract: BACKGROUND
  Folate receptor-α regulates cellular uptake of folates and antifolates (eg, pemetrexed) and is frequently expressed in pulmonary adenocarcinoma. EGFR is an established therapeutic target in NSCLC. Therapies targeting FRA or EGFR are available. The association between FRA and EGFR expression in advanced NSCLC has not been explored. Combining therapeutic FRA antibodies with an EGFR inhibitor might be beneficial, if both of the targets are significantly coexpressed.
  
  
  METHODS
  Specimens from 160 advanced NSCLC patients receiving pemetrexed-based chemotherapy were assessed for membranous FRA and EGFR protein expression using immunohistochemistry and the Hybrid (H)-score. EGFR (exons 18-21) and Kirsten RNA-associated rat sarcoma 2 virus (exon 2) mutations were determined. Results were correlated to patients' clinicopathological data, progression-free survival (PFS), and overall survival (OS).
  
  
  RESULTS
  Forty-seven patients (29%) had tumors with strong FRA and EGFR expression, but no statistically significant correlation was seen between protein levels of FRA and EGFR. High membranous FRA expression (H-score ≥ 20) was associated with prolonged PFS (5.5 vs. 3.4 months; hazard ratio [HR], 0.6060; P = .0254) and improved OS (12.1 vs. 6.4 months; HR, 0.5726; P = .0076).
  
  
  CONCLUSIONS
  Survival times are improved in NSCLC patients whose tumors show strong membranous FRA expression. No statistical correlation between membranous FRA and EGFR expression was demonstrated in advanced NSCLC, but 47 patients (29%) had higher expression of both of the receptors and could be suitable for combined targeted therapies.
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Christoph
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Reyna-Asuncion
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Biftu
authors.initials: B
authors.lastname: Hassan
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Cindy
authors.initials: C
authors.lastname: Tran
authors.affiliation: Morphotek Inc, Exton, PA.
authors.forename: Julia D
authors.initials: JD
authors.lastname: Maltzman
authors.affiliation: Morphotek Inc, Exton, PA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: O'Shannessy
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Gauler
authors.affiliation: Department of Pathology and Neuropathology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Jeremias
authors.initials: J
authors.lastname: Wohlschlaeger
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Wilfried E
authors.initials: WE
authors.lastname: Eberhardt
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO. Electronic address: fred.hirsch@ucdenver.edu.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D058975:Folate Receptor 1 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000068437:Pemetrexed; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D058975:Folate Receptor 1; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D066246:ErbB Receptors
keywords: Antifolate chemotherapy; Combination of targeted agents; Correlation of receptor expression; Predictive biomarker; Therapeutic antibody