E‐cadherin expression in human epithelial ovarian cancer and normal ovary

Abstract

The ovarian surface epithelium (OSE) is the origin of the majority of human ovarian cancers. These adenocarcinomas are characterized by initial local growth followed by spreading into the peritoneal cavity at later stages of tumor progression. The cell-adhesion molecule E-cadherin (E-cad) plays an important role in maintaining tissue integrity. Disappearance or impaired function of E-cad have often been associated with tumor formation and invasion in vivo and in vitro. The cell-specific expression of E-cad was investigated in normal human ovaries (n 5 12), in benign (n 5 5) and borderline (n 5 4) ovarian epithelial tumors and in adenocarcinomas of different stages and histological grades (n 5 18), by immunohistochemistry and immunoblotting. An ovarian cancer cell line (NIH-OVCAR3) was used as a reference. The epithelial origin of the cells was confirmed with cytokeratin (AE1/AE3) staining. In normal ovaries, the expression of E-cad was limited to inclusion cysts or deep clefts lined with OSE, whereas no staining of the OSE could be demonstrated at the surface of the ovary. In contrast, benign and borderline tumors uniformly expressed E-cad. This was observed in malignant tumors of all stages despite their degree of differentiation. E-cad was also present in metastasis from such tumors. The cell-specific expression of E-cad in inclusion cysts of normal ovaries and in epithelial layers of borderline tumors indicates a role for E-cad in the early events of the progression to a malignant phenotype. E-cad was not downregulated in later stages of ovarian cancer progression. Int.

Tight junction formation in epithelial ovarian adenocarcinoma

“…However, in the same study, it was shown that neither E‐cadherin (5) nor claudin‐4 are expressed in the normal OSE. On the contrary, we and others have shown up regulation of mRNA and corresponding proteins in EOC compared to surface‐OSE (12–19). In addition, over‐expression of claudin‐3 and claudin‐4 in cultured OSE rendered a more invasive cell, while blocking claudin‐3 and claudin‐4 production in EOC actually reduced invasiveness (20).…”

“…OSE is also found lining small cyst formations in the ovarian stroma, where the tumours are first encountered during benign or early stages of the disease (1), (3), (22). The OSE within cysts expresses E‐cadherin, claudin‐3 and claudin‐4, and has a more epithelial‐like morphology than surface‐OSE, which lack these typical epithelial markers (12), (13), (18). OSE seems to go through mesothelial–epithelial conversion in the ovarian stroma before transformation into tumour cells of quite diverse and heterogenic histology with main subgroups, such as serous, mucinous, endometrioid, clear cell and undifferentiated adenocarcinomas of the ovary (22).…”

Prophylactic oophorectomy

“…This study further analyzes morphologic and biochemical features of ovaries considered at high risk for developing ovarian carcinoma using immunohistochemical expression patterns of the following markers: CA‐125, p53, Mib‐1, Bcl‐2, and E‐cadherin. All of these markers have been reported previously to show significant differences in expression in normal/benign ovarian surface epithelium compared with ovarian carcinoma tissues 13–20. Our hypothesis was that expression patterns of these markers in high‐risk ovaries may deviate from normal ovaries and assume a pattern similar to that seen in carcinomas.…”

Use of E-cadherin and CD44 aids in the differentiation between reactive mesothelial cells and carcinoma cells in pelvic washings

“…Similar to other members of the cadherin family, E‐cadherin binds to the actin‐based cytoskeleton by a group of proteins called catenins, forming the zonula adherens 29, 39. Increased E‐cadherin expression has been demonstrated in both benign and malignant ovarian epithelial neoplasms 53, 54. In the normal ovary, E‐cadherin expression is either absent or present inconsistently on the ovarian surface but is increased in surface invaginations and epithelial inclusion cysts 53–55.…”

“…Increased E‐cadherin expression has been demonstrated in both benign and malignant ovarian epithelial neoplasms 53, 54. In the normal ovary, E‐cadherin expression is either absent or present inconsistently on the ovarian surface but is increased in surface invaginations and epithelial inclusion cysts 53–55. The latter are the sites of frequent metaplastic and dysplastic changes 56–59.…”