The role of hepatocyte nuclear factor-1beta in the pathogenesis of clear cell carcinoma of the ovary.
OBJECTIVE
Clear cell carcinoma (CCC) of the ovary has a number of features distinguishing it from other epithelial ovarian carcinomas (EOC) because of its characteristic histology and biology, frequent concurrence with endometriotic lesion, and highly chemoresistant nature resulting in an extremely poor prognosis. The incidence of CCC has been steadily increasing in Japan. They comprise approximately 20% of all EOC. Understanding the mechanisms of CCC development and elucidating pathogenesis and pathophysiology are intrinsic to prevention and effective therapies for CCC.


METHODS
This article reviews the English language literature for biology, pathogenesis, and pathophysiological studies on endometriosis-associated EOC. Several data are discussed in the context of endometriosis and CCC biology.


RESULTS
Recent studies based on genome-wide expression analysis technology have noted specific expression of hepatocyte nuclear factor-1beta (HNF-1beta) in endometriosis and CCC, suggesting that early differentiation into the clear cell lineage takes place in the endometriosis. The HNF-1beta-dependent pathway of CCC will be discussed, which are providing new insights into regulation of apoptosis and glycogen synthesis and resistance of CCC to anticancer agents.


CONCLUSIONS
This review summarizes recent advances in the HNF-1beta and its target genes; the potential challenges to the understanding of carcinogenesis, pathogenesis, and pathophysiology of CCC; and a possible novel model is proposed.
Kobayashi
Hiroshi
H
Department of Obstetrics and Gynecology, Nara Medical University, Japan. hirokoba@naramed-u.ac.jp
Yamada
Yoshihiko
Y
Kanayama
Seiji
S
Furukawa
Naoto
N
Noguchi
Taketoshi
T
Haruta
Shoji
S
Yoshida
Shozo
S
Sakata
Mariko
M
Sado
Toshiyuki
T
Oi
Hidekazu
H
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000378:metabolism*; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*
D051539:Hepatocyte Nuclear Factor 1-beta