Clear cell
tumors of the ovary are frequently associated with ovarian
endometriosis. Clinicopathologically, it has been suggested that clear cell
tumors develop from
endometriosis, but there has been little molecular evidence supporting this speculation. Microarray analysis revealed recently that
hepatocyte nuclear factor-1beta (HNF-1beta) was significantly upregulated in clear cell
carcinoma of the ovary. In the present study, we examined 30 clear cell
tumors (26 malignant, three borderline, and one benign) and 40 endometriotic
cysts to clarify if differentiation into the clear cell lineage already begins in ovarian
endometriosis. All of the 30 clear cell
tumors, including borderline and benign ones, showed immunohistochemical expression of
HNF-1beta in the nucleus, while other types of ovarian epithelial
tumors (endometrioid, serous, mucinous, and Brenner
tumors) rarely expressed it. Among 30 clear cell
tumors, 17 (56%) cases were associated with
endometriosis, and endometriotic epithelium was identified in 12 cases. In nine of the 12 cases, distinct nuclear immunostaining for
HNF-1beta was detected in the endometriotic epithelium, as well as in the clear cell
tumor.
HNF-1beta expression was observed either in atypical
endometriosis (four cases), or in
endometriosis of a reactive nature (five cases). Furthermore, 16 of 40 (40%) endometriotic
cysts without a
neoplasm also expressed
HNF-1beta, and the expression was almost exclusively observed in the epithelium showing inflammatory atypia. Our results indicate that
HNF-1beta is an excellent molecular marker for ovarian clear cell
tumors, including benign, borderline and malignant lesions. Early differentiation into the clear cell lineage takes place in ovarian
endometriosis, not only in atypical
endometriosis, but also in
endometriosis with degenerative and regenerative changes, and this is probably responsible for the frequent occurrence of clear cell
carcinoma in ovarian
endometriosis.