From Phil Cagle and colleagues: Folate Receptor in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: Potential Target for Folate-Linked Therapeutic Agents

http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2012-0176-OA

Folate Receptor in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: Potential Target for Folate-Linked Therapeutic Agents

Philip T. Cagle, MD; Qihui “Jim” Zhai, MD; Linda Murphy, HT(ASCP); Philip S. Low, PhD

From the Department of Pathology and Genomic Medicine, The Methodist Hospital, Houston, Texas (Dr Cagle); the Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio (Dr Zhai); the Women's Cancer Program/CER Oncology Laboratory, Mayo Clinic, Rochester, Minnesota (Ms Murphy); and the Department of Chemistry, Purdue University, West Lafayette, Indiana (Dr Low).

Context.—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.

Design.—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.