title: Folate Receptor Alpha Expression in Platinum Resistant/Refractory Ovarian Carcinomas and Primary Endocervical Adenocarcinomas.
abstract: Treatment of advanced stage ovarian carcinoma is challenging, and despite surgical treatment and chemotherapy, the 5-year survival rate is estimated around 30%. Early recurrence and resistance to platinum-based chemotherapy are associated with poor prognosis and limited response to available second-line chemotherapy. The relative incidence of endocervical adenocarcinoma (EAC) compared with squamous cell carcinoma is increasing. Although the first-line treatment modality for early stage EAC is surgical resection, for locally advanced disease chemoradiation or neoadjuvant chemotherapy is used. Recently, folate along with its receptor alpha (FRA) has been studied as a potential target in gynecologic malignancy. The objective of this study was to elucidate FRA expression in chemotherapy resistant ovarian cancer and primary EAC.
  
  
  
  FRA expression was evaluated in tissue samples in an epithelial ovarian tumor microarray and 2 study groups: platinum resistant ovarian cancer and primary EAC. Staining intensity was analyzed with a semiquantitative staining algorithm.
  
  
  
  FRA expression was positive in 32 of 40 (80%) ovarian tumors in the control group. In the platinum resistant ovarian cancer group, FRA was expressed in all 30 samples with moderate to strong staining. None of the EAC samples stained positive for FRA expression.
  
  
  
  FRA expression occurs frequently in epithelial ovarian cancer. Our data supports that FRA expressions are maintained after chemotherapy treatment. Folate targeted therapies may be most useful in patients with chemotherapy resistant disease based on high levels of FRA expression in these tumors. There is likely no benefit to folate therapy as an adjuvant treatment in EAC.
authors.affiliation: Departments of Obstetrics and Gynecology.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Rubinsak
authors.affiliation: Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Departments of Obstetrics and Gynecology.
authors.forename: Namita
authors.initials: N
authors.lastname: Khanna
authors.affiliation: Departments of Obstetrics and Gynecology.
authors.forename: Ira R
authors.initials: IR
authors.lastname: Horowitz
authors.affiliation: Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Krisztina Z
authors.initials: KZ
authors.lastname: Hanley
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D058975:Folate Receptor 1 / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010984:Platinum; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D009363:Neoplasm Proteins; D010984:Platinum