Differential expression of hypoxia-inducible protein 2 among different histological types of epithelial ovarian cancer and in clear cell adenocarcinomas.
OBJECTIVE
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.
Nishimura
Sadako
S
Department of Obstetrics and Gynecology, Osaka City General Hospital, Osaka, Japan.
Tsuda
Hiroshi
H
Ito
Kiyoshi
K
Takano
Masashi
M
Terai
Yoshito
Y
Jobo
Toshiko
T
Kigawa
Junzo
J
Sugiyama
Toru
T
Yaegashi
Nobuo
N
Aoki
Daisuke
D
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan / Q000453:epidemiology; D007680:Kidney Neoplasms / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality; D014594:Uterine Neoplasms / Q000378:metabolism; D055815:Young Adult
D014408:Biomarkers, Tumor; C405620:HILPDA protein, human; D009363:Neoplasm Proteins