title: Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma.
abstract: Distinguishing primary ovarian carcinoma, particularly endometrioid and mucinous subtypes, from metastatic colorectal carcinoma to the ovary is often difficult on histologic examination alone. Recently, three immunohistochemical markers CDX2, a homeobox gene encoding an intestine-specific transcription factor; alpha-methylacyl-CoA racemase (AMACR/P504S), a mitochondrial and peroxisomal enzyme with fairly restricted expression in selective tumors and beta-catenin, an adenomatous polyposis coli (APC) mutation product resulting in activation of the Wnt pathway, have been reported to have specific and sensitive expression in colorectal carcinomas. We evaluated a panel consisting of antibodies to CDX2, beta-catenin and P504S in 23 primary ovarian adenocarcinomas (13 mucinous and 10 endometrioid) and compared the findings to 22 metastatic colorectal adenocarcinomas (seven mucinous and 15 nonmucinous tumors with endometrioid-like morphology hereafter referred to as pseudo-endometrioid) to the ovary stained with the same panel. Twenty (91%) metastatic tumors expressed at least two markers and seven (32%) expressed all three. In contrast, only three (13%) primary ovarian tumors expressed at least two markers and none expressed all three. Strong (2+, 3+) and diffuse (>40%) expression for CDX2 was noted in 21 (95%) metastatic tumors and five (22%) primary ovarian tumors (three mucinous, two endometrioid). P504S was similarly expressed in seven (32%) metastatic and none of the primary ovarian carcinomas. Nuclear expression of beta-catenin was noted in 13 (59%) metastatic tumors and in eight cases (36%), it was diffuse and strong. In contrast, four (19%) primary tumors showed nuclear expression of this protein with only one (5%) case expressing it in a diffuse pattern. Immunohistochemical expression of gene products and enzymes of colorectal carcinogenesis in some primary ovarian carcinomas suggest that the morphologic similarities between colorectal and mucinous/endometrioid carcinoma of the ovary extends to the genetic level, although differences in the level of expression exist between these tumors. Diffuse expression of all three markers (CDX2, beta-catenin and P504S) in a tumor in the ovary was found to be virtually diagnostic of metastasis from a colorectal primary in this study.
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA. slogani@emory.edu
authors.forename: Sanjay
authors.initials: S
authors.lastname: Logani
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Paula M
authors.initials: PM
authors.lastname: Arnell
authors.forename: Mahul B
authors.initials: MB
authors.lastname: Amin
authors.forename: Robert H
authors.initials: RH
authors.lastname: Young
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis*; D000071616:CDX2 Transcription Factor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000556:secondary*; D003598:Cytoskeletal Proteins / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D019998:Racemases and Epimerases / Q000032:analysis; D015534:Trans-Activators / Q000032:analysis; D051176:beta Catenin
chemical_list: D015415:Biomarkers; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase