title: Protein profiling of ovarian cancers by immunohistochemistry to identify potential target pathways.
abstract: BACKGROUND
  To determine the protein expression profile (PEP) of primary and recurrent ovarian cancer patients in order to predict therapeutic targets for chemotherapy.
  
  
  METHODS
  Tissue samples were submitted for PEP in two formats, including formalin-fixed paraffin-embedded tissue for immunohistochemistry (IHC) and fresh frozen tissue for oligonucleotide microarray (MA) gene expression assays. Specimens were analyzed for 18 protein markers and 88 MA genes. A series of Generalized Linear Models (GLM) was used to predict the proportion of positive results by histology for each biomarker.
  
  
  RESULTS
  Four hundred and twenty-eight specimens were analyzed for IHC and 67 specimens for MA analysis. The majority of specimens, 82%, were serous histology and 35.3% of specimens were poorly differentiated. Sixty percent of specimens were advanced stage, 62% were from a primary diagnosis, and 53% were obtained from a metastatic site. BCRP, ER, MGMT, and RRM1 proteins were overexpressed in 85%, 47%, 93%, and 47% of serous carcinomas, respectively. The MGMT and RRM1 biomarkers were significantly overexpressed in serous (p < .001) and endometrioid (p = .01) histologies when compared to clear cell histology. MGMT was significantly elevated in 93% of serous and endometrioid samples, compared to 62% of samples with clear cell histology. Those proteins most often underexpressed included Her2/neu, SPARC, and c-kit, seen in less than 1%, 4%, and 5% of specimens, respectively.
  
  
  CONCLUSIONS
  PEP is a reliable and effective way of analyzing ovarian cancer specimens. PEP target identification does not appear to vary significantly with site evaluated, ovarian or other abdominal pelvic tissue, or primary versus recurrent disease. Variability in the expression of drug targets, including BCRP, ER, MGMT, and RRM1 could impact decision making pertaining to which therapeutic strategies carry the best chances for controlling disease.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Arizona Cancer Center, 500 W. Thomas Road, Suite 600, Phoenix, AZ 85013 USA ; Creighton University School of Medicine at Dignity Health St. Joseph's Hospital and Medical Center, 500 W. Thomas Road, Suite 600, Phoenix, AZ 85013 USA.
authors.forename: Cassandra D
authors.initials: CD
authors.lastname: Foss
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Dalton
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Arizona Cancer Center, 500 W. Thomas Road, Suite 600, Phoenix, AZ 85013 USA ; Creighton University School of Medicine at Dignity Health St. Joseph's Hospital and Medical Center, 500 W. Thomas Road, Suite 600, Phoenix, AZ 85013 USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Arizona Cancer Center, 500 W. Thomas Road, Suite 600, Phoenix, AZ 85013 USA ; Creighton University School of Medicine at Dignity Health St. Joseph's Hospital and Medical Center, 500 W. Thomas Road, Suite 600, Phoenix, AZ 85013 USA.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Chase
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Arizona Cancer Center, 500 W. Thomas Road, Suite 600, Phoenix, AZ 85013 USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Farley
keywords: Immunohistochemistry; Ovarian cancer; Protein profiling