Immunohistochemical Analysis of CD44s and CD44v6 in Endometriosis and Adenomyosis: Comparison with normal, hyperplastic, and malignant endometrium

Abstract

The expression patterns of CD44s and CD44v6 were immunohistochemically compared with those of normal, hyperplastic and malignant endometrium. In normal endometria (n=37), endometrioses (n=46) and adenomyoses (n=20), the surface and glandular epithelial cells were negative for CD44s and CD44v6 in a proliferative pattern and positive in a secretory pattern, whereas the stroma was only positive for CD44s in both proliferative and secretory patterns. The endometrial hyperplasia (4 simple and 9 complex) had the identical patterns with normal proliferative phase of endometrium. Only one case showing complex hyperplasia with atypia was focally positive for CD44s and CD44v6 in glandular epithelia. CD44s and CD44v6 were positive in all endometrial adenocarcinomas (13), except one CD44s-negative case. In summary, the expressions of CD44s and CD44v6 in endometriosis and adenomyosis recapitulated those of normal cyclic endometrium. The expression patterns in endometrial hyperplasia were similar to those in normal proliferative endometrium, whereas the endometrial adenocarcinoma showed abnormal expressions for CD44s and CD44v6. Thus it was considered that the ectopic endometrium in endometriosis and adenomyosis was not aberrant as in endometrial carcinoma on the aspects of immunohistochemical expressions of CD44s and CD44v6.

CD44 expression in papillary serous endometrial carcinoma

“…CD44 is expressed in normal and malignant tissue in the female reproductive tract, including the uterus. Normal endometrium lacks CD44 in the proliferative phase but is CD44‐positive in the secretory phase ( 5 ) . Hyperplastic endometrial tissue mimicks proliferative endometrium (CD44‐negative) but malignant endometrial cells in general overexpress CD44 ( 3,5 ) .…”

“…Five classes of cell adhesion molecules exist; two involving adhesion of like cells (cadherins and Ig‐superfamily CAMs), two concerned with connections of dissimilar cell lines (selectins and mucins) and one (integrins) mediating cell‐matrix adhesions ( 4 ) . Various Ig‐superfamily CAMs exist, but homing cell adhesion molecule (HCAM), otherwise known as CD44, is commonly seen in endometrial tissues ( 5,6 ) . CD44 expression is present in endometrial cancers as well, and loss of CD44 expression has been correlated with a more aggressive course in some studies ( 7,8 ) .…”

High soluble CD44 concentration in peritoneal fluid in endometriosis

“…It has been reported that CD44 is expressed not only in endometrial cells but also in endometriosis lesions (3,4). Moreover, Dechaud et al, using the in vitro adhesion model, reported that interaction between endometrial cell-associated CD44 and mesothelial cell-associated HA might be crucial for the initiation of endometriosis (6).…”

“…Soluble CD44 can also bind to HA, acting as a competitive inhibitor for membrane-bound CD44. Although there is a growing body of evidence that CD44 is involved in endometriosis (3,4), the importance of sCD44 is still unknown. As a first step, we investigated the sCD44 expression in the peritoneal fluid (PF) of patients with endometriosis.…”