Elsevier

Human Pathology

Volume 35, Issue 8, August 2004, Pages 1014-1021
Human Pathology

Original contributions
Expression of candidate tumor markers in ovarian carcinoma and benign ovary: Evidence for a link between epithelial phenotype and neoplasia☆

https://doi.org/10.1016/j.humpath.2004.04.014Get rights and content

Abstract

EpCAM, epithelial membrane antigen (EMA)-mucin 1 (MUC1), mesothelin, and CD9 have been reported to be overexpressed at the RNA level in ovarian carcinomas. By using immunohistochemistry, we profiled the protein expression of these gene products in ovarian carcinoma tissues and compared them with benign ovarian surface epithelium (OSE) and cortical inclusion cysts (CICs). Immunoreactivity for EMA and calretinin were used to define epithelial and mesothelial differentiation in nontumor tissues, respectively. Papillary serous (n = 16) and endometrioid (n = 10) tumors were immunopositive for EMA/MUC1 (100%), mesothelin (75% and 30%, respectively), CD9 (88% and 90%, respectively), and EpCAM (100%). All ovarian carcinomas and carcinoma cell lines tested were negative for calretinin. In nonneoplastic ovary, both OSE and CICs ranged from flat-to-cuboidal to stratified and ciliated in appearance. OSE with a cuboidal morphology had a similar immunoreactivity as omental peritoneum, expressing calretinin, mesothelin, and CD9. In contrast, CICs with stratified and ciliated epithelium show expression patterns similar to those in fallopian tubes. They frequently expressed EMA, EpCAM, mesothelin, and CD9. This immunophenotype is preserved in ovarian carcinomas, suggesting that Müllerian metaplasia signals the acquisition of these markers and that their expression is maintained in ovarian carcinomas that originate from this epithelium.

Section snippets

Materials and methods

Genomewide experimental approaches have been applied to the study of ovarian cancer. Attempts to identify genes involved in ovarian tumorigenesis have used primary human ovarian tumors and cell lines in a wide array of experimental methodologies, including differential display, serial analysis of gene expression, global gene expression profiling using cDNA arrays, comparative genomic hybridization, 2-dimensional gel electrophoresis of cellular proteins, and proteomic analysis of serum proteins.

Epithelial versus mesothelial antigens

To establish internal controls for these studies, we examined the expression patterns of calretinin and EMA (MUC1). Calretinin is a calcium-binding protein that is expressed in mesothelial cells and mesotheliomas but not in adenocarcinomas of various sites.18, 19 Recent studies have shown that calretinin is expressed robustly in OSE and its invaginations and in CICs lined by flat-to-cuboidal epithelium.20, 21 In contrast, EMA is a high molecular weight transmembrane glycoprotein expressed in

Discussion

In human ovarian carcinomas, overexpression of EMA/MUC1, EpCAM, mesothelin, and CD9 has been shown in some studies to occur at the RNA level (see Table 1). In this article, we have verified that the corresponding proteins are highly expressed in both serous and endometrioid carcinomas. Calretinin, a marker of mesothelial cells and OSE, was not expressed in these tumors and served as a control in these experiments. Expression of EMA/MUC1, EpCAM, and CD9 was present in both endometrioid and

Acknowledgements

The authors thank Dr. Sam Mok (Brigham and Women’s Hospital, Boston, MA) for the kind gift of the human ovarian surface epithelial cell lines, Cathy Quigley (Brigham and Women’s Hospital, Boston, MA) for her expertise in tissue immunohistochemistry, and Drs. Michael Seiden, Patrick Sluss, Steve Skates, David Livingston, and Paola Vermeer for discussion and support.

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    ☆

    Supported in part by an Individual Investigator Award from the Ovarian Cancer Research Fund (R.D.) and a grant from the Ovarian Cancer Research Training Program at the Dana-Farber/Harvard Cancer Center (DAMD17-03-1-0161).

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