title: Cytokeratin expression in gastrointestinal stromal tumors: morphology, meaning, and mimicry.
abstract: BACKGROUND
  Gastrointestinal stromal tumors (GISTs) are biologically distinctive neoplasms harboring KIT and PDGFRA mutations. Cytokeratin expression in GISTs is an under-recognized diagnostic pitfall, especially in high grade GISTs with limited biopsy material and from metastatic sites.
  
  
  METHODS
  We evaluated the histomorphology and expression of four 'broad-spectrum' cytokeratin markers, AE1-AE3, CAM 5.2, MNF-116, and 34βE12 in 64 GISTs diagnosed over a 68-month period. Individual cytokeratins 5, 6, 7, 8, 14, 17, 18, 19, and 20 were investigated in the 'broad-spectrum' cytokeratin-positive GISTs.
  
  
  RESULTS
  Of 64 GISTs, 10 (15%) demonstrated cytokeratin immunopositivity. All 10, considered high risk by the National Institutes of Health consensus approach, were immunopositive for CAM 5.2 and MNF-116. Seven were AE1-AE3 immunopositive. Cytokeratins 8 and 18 were confirmed in 10 and 9 GISTs, respectively. One GIST demonstrated biphasic morphology with cytokeratin immunonegativity in low-grade spindle and immunopositivity in high-grade epithelioid foci. KIT and PDGFRA mutational analysis, undertaken in 5/10 cytokeratin-positive GISTs, harbored KIT exon 11 mutations.
  
  
  CONCLUSIONS
  We hypothesize that cytokeratin expression exclusively in high risk GISTs is a consequence of tumor progression. Given the increasing number of commercially available broad-spectrum cytokeratin immunomarkers, including those reacting with cytokeratins 8 and 18, cytokeratin-positive GISTs must be differentiated from carcinomas, melanomas, and a range of cytokeratin-positive sarcomas to ensure optimal patient management and prognostication.
authors.affiliation: Department of Anatomical Pathology, School of Laboratory Medicine and Clinical Sciences, University of KwaZulu Natal & National Health Laboratory Service, South Africa.
authors.forename: Yetish
authors.initials: Y
authors.lastname: Sing
authors.forename: Pratistadevi K
authors.initials: PK
authors.lastname: Ramdial
authors.forename: Amsha
authors.initials: A
authors.lastname: Ramburan
authors.forename: Vikash
authors.initials: V
authors.lastname: Sewram
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D007633:Keratins / Q000032:analysis*; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D007633:Keratins