title: Immunohistochemical expression of CDX2 in primary ovarian mucinous tumors and metastatic mucinous carcinomas involving the ovary: comparison with CK20 and correlation with coordinate expression of CK7.
abstract: Recent studies have demonstrated conflicting results regarding the value of CDX2 for distinguishing primary ovarian mucinous tumors from metastatic mucinous carcinomas in the ovary. Utility of coordinate expression of cytokeratins 7 and 20 is restricted to distinction of ovarian mucinous tumors from lower gastrointestinal tract metastases and data comparing coordinate expression of all three markers is limited. Immunohistochemical studies were performed to compare expression of CDX2 and cytokeratin 20, both markers of intestinal differentiation, in conjunction with coordinate expression of cytokeratin 7, in 90 mucinous tumors involving the ovary: 42 primary ovarian mucinous tumors (31 atypical proliferative (borderline) mucinous tumors (gastrointestinal type), 11 mucinous carcinomas) and 48 metastatic mucinous carcinomas of upper (pancreaticobiliary tract: 14; stomach: five) and lower (colon and rectum: 25; appendix: four) gastrointestinal tract origin. Primary ovarian tumors expressed CDX2 (40%) less frequently than cytokeratin 20 (83%) (P<0.0001). CDX2 expression in primary ovarian tumors (40%) was lower than CDX2 expression in metastatic carcinomas of both upper (74%; P=0.016) and lower gastrointestinal tract origin (90%; P<0.0001). Cytokeratin 20 expression was similar in primary ovarian tumors (83%) and metastases of upper (89%; P=0.071) and lower gastrointestinal tract origin (93%; P=0.29). Thus, as a single marker CDX2 offers some advantage over cytokeratin 20 because it is less frequently positive in primary ovarian tumors. In the almost universally cytokeratin 7-positive primary ovarian tumors and metastases of upper gastrointestinal tract origin, CDX2 coordinate expression was less common in primary ovarian tumors (36%) than in metastases of upper gastrointestinal tract origin (63%) (P=0.022) whereas cytokeratin 20 coordinate expression was identical in both tumor types (79%). In the almost universally cytokeratin 7-negative metastases of lower gastrointestinal tract origin, coordinate expression of CDX2 (83%) and cytokeratin 20 (86%) were equivalent (P=1.00). CDX2 was comparable to cytokeratin 20 in distinguishing metastases of lower gastrointestinal tract origin (usually cytokeratin 7-negative and CDX2/cytokeratin 20 positive) from primary ovarian tumors and metastases of upper gastrointestinal tract origin (usually cytokeratin 7-positive and CDX2/cytokeratin 20 variable). CDX2 provided some advantage over cytokeratin 20 for distinguishing primary ovarian mucinous tumors from metastases of upper but not lower gastrointestinal tract origin; however, the advantage in the former was limited due to the occurrence of shared coordinate expression profiles in both tumor types. Cytokeratin 7 provides the predominant discriminatory value among these markers yet is limited to distinction of primary ovarian tumors from metastases of lower gastrointestinal tract origin.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. rvang1@jhmi.edu
authors.forename: Russell
authors.initials: R
authors.lastname: Vang
authors.forename: Allen M
authors.initials: AM
authors.lastname: Gown
authors.forename: Lee-Shu-Fune
authors.initials: LS
authors.lastname: Wu
authors.forename: Todd S
authors.initials: TS
authors.lastname: Barry
authors.forename: Darren T
authors.initials: DT
authors.lastname: Wheeler
authors.forename: Anna
authors.initials: A
authors.lastname: Yemelyanova
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Seidman
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Ronnett
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology / Q000556:secondary; D014408:Biomarkers, Tumor / Q000032:analysis*; D000071616:CDX2 Transcription Factor; D003937:Diagnosis, Differential; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000737:chemistry* / Q000473:pathology; D018398:Homeodomain Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000032:analysis; D053552:Keratin-7 / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology / Q000556:secondary
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C507499:KRT20 protein, human; C507497:KRT7 protein, human; D053554:Keratin-20; D053552:Keratin-7