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.
Department of Obstetrics and Gynecology, Osaka City General Hospital, Osaka, Japan.
Sadako
S
Nishimura
Hiroshi
H
Tsuda
Kiyoshi
K
Ito
Masashi
M
Takano
Yoshito
Y
Terai
Toshiko
T
Jobo
Junzo
J
Kigawa
Toru
T
Sugiyama
Nobuo
N
Yaegashi
Daisuke
D
Aoki
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