Article Text

Download PDFPDF
Differential Expression of Hypoxia-Inducible Protein 2 Among Different Histological Types of Epithelial Ovarian Cancer and in Clear Cell Adenocarcinomas
  1. Sadako Nishimura, MD, PhD*,
  2. Hiroshi Tsuda, MD, PhD,
  3. Kiyoshi Ito, MD, PhD,
  4. Masashi Takano, MD, PhD§,
  5. Yoshito Terai, MD, PhD,
  6. Toshiko Jobo, MD, PhD,
  7. Junzo Kigawa, MD, PhD**,
  8. Toru Sugiyama, MD, PhD††,
  9. Nobuo Yaegashi, MD, PhD and
  10. Daisuke Aoki, MD, PhD
  1. *Department of Obstetrics and Gynecology, Osaka City General Hospital, Osaka;
  2. Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo;
  3. Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai;
  4. §Department of Obstetrics and Gynecology, National Defence Medical College, Tokorozawa;
  5. Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki;
  6. Department of Obstetrics and Gynecology, School of Medicine Kitasato University, Sagamihara;
  7. **Department of Obstetrics and Gynecology, Tottori University, Yonago; and
  8. ††Department of Obstetrics and Gynecology, Iwate Medical University, Morioka, Japan.
  1. Address correspondence and reprint requests to Hiroshi Tsuda, MD, PhD, Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjyuku-ku, Tokyo, Japan 160-8582. E-mail: htsud{at}


Objectives: Epithelial ovarian cancer (EOC) can be classified into 5 major histological types. Among them, clear cell adenocarcinoma (CCC) has a poor response to chemotherapy and poor prognosis compared with other histological types. Previously, we reported that the hypoxia-inducible protein 2 (HIG2) gene might be a new biomarker for CCCs, based on its expression profile. In this study, we generated a polyclonal antiserum to HIG2 to explore the use of HIG2 as a predictive biomarker in EOC. In addition, HIG2 expression was evaluated in uterine endometrial and renal CCCs.

Methods: Hypoxia-inducible protein 2 expression was analyzed by immunohistochemistry in formalin-fixed surgical samples from 254 EOC, 17 endometrial, and 29 renal CCC patients.

Results: Hypoxia-inducible protein 2 is expressed in 175 of 254 ovarian cancer cases. Cytoplasmic HIG2 expression is significantly more frequent in ovarian CCC (83.1%) than in serous (54.9%, P = 0.0001), mucinous (40%, P = 0.00002), or endometrioid (58.1%, P = 0.003) adenocarcinoma. The chemoresponse rate was higher in 24 ovarian CCC patients with cytoplasmic HIG2 expression than in 6 CCC patients without HIG2 expression (62.5% [15/24] vs 0% [0/6], P = 0.02). In contrast, there was no relationship between nuclear HIG2 expression and chemoresponse. Cytoplasmic and nuclear HIG2 expressions are significantly more frequent in ovarian and uterine than renal CCC (P = 0.04).

Conclusions: Hypoxia-inducible protein 2 may be used as a marker for early detection of ovarian CCCs or for prediction of response to chemotherapy, but HIG2 expression does not predict survival of patients with CCC.

  • Ovary
  • Clear cell adenocarcinoma
  • Kidney
  • Endometrium

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • This study was supported in part by a grant from Osaka City General Hospital; a grant-in-aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture, Japan (20014024, Keio University); a grant-in-aid from Kurokawa Cancer Research Foundation; a grant-in-aid from the Ministry of Health, Labor and Welfare, Japan; and a 21st Century COE Program special research grant (Tohoku University) from the Ministry of Education Science, Sports and Culture, Japan.

  • The authors have no conflicts of interest to declare.