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The Role of Hepatocyte Nuclear Factor-1β in the Pathogenesis of Clear Cell Carcinoma of the Ovary
  1. Hiroshi Kobayashi, MD, PhD,
  2. Yoshihiko Yamada, MD, PhD,
  3. Seiji Kanayama, MD, PhD,
  4. Naoto Furukawa, MD, PhD,
  5. Taketoshi Noguchi, MD, PhD,
  6. Shoji Haruta, MD,
  7. Shozo Yoshida, MD, PhD,
  8. Mariko Sakata, MD,
  9. Toshiyuki Sado, MD, PhD and
  10. Hidekazu Oi, MD, PhD
  1. Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
  1. Address correspondence and reprint requests to Hiroshi Kobayashi, MD, PhD, Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan. E-mail: hirokoba{at}


Problem: 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.

Method of study: 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-1β (HNF-1β) in endometriosis and CCC, suggesting that early differentiation into the clear cell lineage takes place in the endometriosis. The HNF-1β-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-1β and its target genes; the potential challenges to the understanding of carcinogenesis, pathogenesis, and pathophysiology of CCC; and a possible novel model is proposed.

  • Endometriosis
  • Clear cell carcinoma of the ovary
  • Hepatocyte nuclear factor-1β

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