title: Folate receptor in adenocarcinoma and squamous cell carcinoma of the lung: potential target for folate-linked therapeutic agents.
abstract: BACKGROUND
  Lung cancer is the number one cause of cancer deaths in the United States and globally. The advent of targeted therapies has offered a new treatment paradigm for lung cancer, but currently validated and emerging drugs are effective in only a small minority of lung cancers, predominantly adenocarcinomas. Folate receptors can serve as targets for drugs attached to folate and are overexpressed in many cancers.
  
  
  OBJECTIVE
  To determine the frequency of folate receptor overexpression in lung cancers of different cell types as potential targets for folate-linked therapy.
  
  
  METHODS
  High-density tissue microarrays were constructed from archival formalin-fixed, paraffin-embedded resection specimens from 188 primary stage I or stage II adenocarcinomas or squamous cell carcinomas of the lung with three 0.1-cm cores from each tumor. Tissue microarrays were immunostained for folate receptor α with mAb343 and the results scored (0 to 1+ = weak expression, 2+ to 3+ = strong expression).
  
  
  RESULTS
  Eighty-four of 117 (72%) of the adenocarcinomas were strongly positive for the folate receptor, and 36 of 71 (51%) of the squamous cell carcinomas were strongly positive for the folate receptor.
  
  
  CONCLUSIONS
  Our data indicate that a large percentage of lung cancers, including squamous cell carcinomas in addition to adenocarcinomas, strongly express folate receptor. This suggests that folate-linked targeted therapy can potentially be used to treat the majority of lung cancers, both adenocarcinomas and, particularly, squamous cell carcinomas, that do not respond to current targeted therapies.
authors.affiliation: Department of Pathology and Genomic Medicine, The Methodist Hospital, Houston, Texas 77030, USA. pcagle@tmhs.org
authors.forename: Philip T
authors.initials: PT
authors.lastname: Cagle
authors.forename: Qihui Jim
authors.initials: QJ
authors.lastname: Zhai
authors.forename: Linda
authors.initials: L
authors.lastname: Murphy
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D058975:Folate Receptor 1 / Q000378:metabolism*; D005492:Folic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D046888:Tissue Array Analysis
chemical_list: C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D005492:Folic Acid