title: Association between IHC and MSI testing to identify mismatch repair-deficient patients with ovarian cancer.
abstract: OBJECTIVE
  In epithelial ovarian cancer, concordance between results of microsatellite instability (MSI) and immunohistochemical (IHC) testing has not been demonstrated. This study evaluated the association of MSI-high (MSI-H) status with loss of expression (LoE) of mismatch repair (MMR) proteins on IHC and assessed for potential factors affecting the strength of the association.
  
  
  METHODS
  Tumor specimens from three population-based studies of epithelial ovarian cancer were stained for MMR proteins through manual or automated methods, and results were interpreted by one of two pathologists. Tumor and germline DNA was extracted and MSI testing performed. Multivariable logistic regression models were fitted to predict loss of IHC expression based on MSI status after adjusting for staining method and reading pathologist.
  
  
  RESULTS
  Of 834 cases, 564 (67.6%) were concordant; 41 were classified as MSI-H with LoE and 523 as microsatellite stable (MSS) with no LoE. Of the 270 discordant cases, 83 were MSI-H with no LoE and 187 were MSS with LoE. Both IHC staining method and reading pathologist were strongly associated with discordant results.
  
  
  CONCLUSIONS
  Lack of concordance in the current study may be related to inconsistencies in IHC testing methods and interpretation. Results support the need for validation studies before routine screening of ovarian tumors is implemented in clinical practice for the purpose of identifying Lynch syndrome.
authors.affiliation: 1 Department of Biostatistics, H. Lee Moffitt Cancer Center , Tampa, Florida.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Deborah
authors.initials: D
authors.lastname: Cragun
authors.forename: Zachary
authors.initials: Z
authors.lastname: Thompson
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.forename: Santo V
authors.initials: SV
authors.lastname: Nicosia
authors.forename: Mohammad
authors.initials: M
authors.lastname: Akbari
authors.forename: Shiyu
authors.initials: S
authors.lastname: Zhang
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.forename: Steven
authors.initials: S
authors.lastname: Narod
authors.forename: Joellen
authors.initials: J
authors.lastname: Schildkraut
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.forename: Tuya
authors.initials: T
authors.lastname: Pal
mesh_terms: D000368:Aged; D020137:Base Pair Mismatch; D000077216:Carcinoma, Ovarian Epithelial; D004260:DNA Repair; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053842:Microsatellite Instability; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*