Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma

Mod Pathol. 2005 Jan;18(1):19-25. doi: 10.1038/modpathol.3800260.


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.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Biomarkers / analysis*
  • CDX2 Transcription Factor
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / secondary*
  • Cytoskeletal Proteins / analysis
  • Diagnosis, Differential
  • Female
  • Homeodomain Proteins / analysis
  • Humans
  • Immunohistochemistry
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Racemases and Epimerases / analysis
  • Trans-Activators / analysis
  • beta Catenin


  • Biomarkers
  • CDX2 Transcription Factor
  • CDX2 protein, human
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Homeodomain Proteins
  • Trans-Activators
  • beta Catenin
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase