Differential expression of hypoxia-inducible protein 2 among different histological types of epithelial ovarian cancer and in clear cell adenocarcinomas.

Abstract

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.

• Authors: Sadako Nishimura, Hiroshi Tsuda, Kiyoshi Ito, Masashi Takano, Yoshito Terai, Toshiko Jobo, Junzo Kigawa, Toru Sugiyama, Nobuo Yaegashi, Daisuke Aoki
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 20 Issue 2 Pg. 220-6 (Feb 2010) ISSN: 1525-1438 [Electronic] England
• PMID: 20134266 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• HILPDA protein, human
• Neoplasm Proteins

Topics

• Adenocarcinoma, Clear Cell (metabolism)
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Female
• Humans
• Immunohistochemistry
• Japan (epidemiology)
• Kidney Neoplasms (metabolism)
• Middle Aged
• Neoplasm Proteins (metabolism)
• Ovarian Neoplasms (metabolism, mortality)
• Uterine Neoplasms (metabolism)
• Young Adult