Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression.

Abstract

Impairment of cell adhesion plays a vital role in tumor progression. E- and N-cadherin, CD9, and KAI1 are all adhesion molecules that have been implicated in the progression of several different tumor types. To help explain the potential role these adhesion molecules have in ovarian cancer, comparisons were made between expression patterns in normal ovary and various grades of primary and metastatic epithelial ovarian cancers. Thirty-two primary and 8 metastatic human ovarian epithelial carcinomas and 18 samples of normal ovarian tissue were examined for adhesion molecule expression using immunohistochemistry. KAI1 and CD9 revealed an inverse relationship between tumor grade and expression levels, characterized by high expression in low-grade tumors and low expression in high-grade tumors and metastases. KAI1 and CD9 also demonstrated a shift in cellular localization from the membrane in grade 1 tumors to the cytoplasm in grade 3 tumors. N-cadherin expression showed a positive trend between expression levels and tumor grade. E-cadherin expression varied little between different tumor grades and metastases. Inclusion cysts (n = 6) and surface invaginations often strongly expressed KAI1, CD9, and E-cadherin. KAI1 expression was variable in ovarian follicles and corpora lutea depending on their stage of development. Although sample size is limited, these findings suggest that progression of ovarian epithelial carcinomas is associated with down-regulation and altered cellular localization of KAI1 and CD9. In addition, variable KAI1 expression during follicular and luteal development suggests that it has a physiological function in the ovary. Further investigation will be needed to see if it is also regulated this way during progression of ovarian cancers.