title: Uncertainty in the utility of immunohistochemistry in mismatch repair protein expression in epithelial ovarian cancer.
abstract: BACKGROUND
  Utility of immunohistochemistry (IHC) for mismatch repair (MMR) protein expression has been demonstrated in colorectal cancer but remains incompletely defined in ovarian cancer. We evaluated MMR protein expression in three population-based samples of epithelial ovarian cancers.
  
  
  METHODS
  IHC staining was performed on full-section (FS) or tissue microarray (TMA) slides for MLH1, MSH2, and MSH6 expression.
  
  
  RESULTS
  Out of 487 cases, 147 and 340 were performed through FS and TMA, respectively. Overall, Loss of Expression (LoE) of at least one MMR protein was observed in 12.7% based on an expression score of ≤3 (on a scale of 9). Notably, LoE was significantly higher in TMAs (17.9%) compared to FS cases (0.7%) (p<0.001).
  
  
  CONCLUSIONS
  A substantial proportion of epithelial ovarian cancers have a loss of MMR protein expression. Protein expression results vary significantly by the tissue sampling methodology utilized, raising concerns about the clinical utility of this test for ovarian tumors.
authors.affiliation: Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. Domenico.Coppola@moffitt.org
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.forename: Santo V
authors.initials: SV
authors.lastname: Nicosia
authors.forename: Andrea
authors.initials: A
authors.lastname: Doty
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Jimmy
authors.initials: J
authors.lastname: Fulp
authors.forename: Zachary
authors.initials: Z
authors.lastname: Thompson
authors.forename: Sanja
authors.initials: S
authors.lastname: Galeb
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Joellen
authors.initials: J
authors.lastname: Schildkraut
authors.forename: Tuya
authors.initials: T
authors.lastname: Pal
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D000077216:Carcinoma, Ovarian Epithelial; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis / Q000096:biosynthesis; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000378:metabolism*; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein