Absence of estrogen receptor-alpha expression in human ovarian clear cell adenocarcinoma compared with ovarian serous, endometrioid, and mucinous adenocarcinoma

The mechanism that regulates growth in ovarian clear cell adenocarcinoma (CCA) is not well understood. A high incidence of concurrent endometriosis with CCA may indicate that estrogen is a growth promotor in CCA. To determine estrogen as a growth promotor, the authors investigated the presence or absence of estrogen receptor-alpha (ER-alpha), ER-beta, progesterone receptor, and dioxin receptor (i.e., aromatic hydrocarbon receptor) in clinically resected ovarian CCA, serous adenocarcinoma (SAC), endometrioid adenocarcinoma (EAC), and mucinous adenocarcinoma (MAC) specimens using an immunohistochemical method. Expression of ER-alpha and ER-beta messenger ribonucleic acid was examined by reverse transcription-polymerase chain reaction in three established CCA cell lines: KK, RMG-1, and HAC-II. None of the surgically resected CCA and CCA cell lines showed positive staining for ER-alpha. Conversely, 97.2% of SACs, 100% of EACs, and 70% of MACs showed positive nuclear staining for ER-alpha (p < 0.001). Conversely, positive ER-beta staining for CCA (39.3%) was similar to that of SAC (41.7%) and MAC (30.0%). EAC (75%) showed a higher expression of ER-beta (p < 0.02). Progesterone receptor was detected in only 10.7% of CCA, compared with SAC and EAC (SAC, 86.1%; EAC, 91.7%; p < 0.01). Aromatic hydrocarbon receptor was detected in all histologic types at an incidence of approximately 50% to 60%. Messenger ribonucleic acid of ER-alpha and ER-beta was not detected in the three CCA cell lines. These findings indicate biologic characteristics that distinguish CCA from other types of ovarian epithelial cancer.