Hypoxic status in ovarian serous and mucinous tumors: relationship between histological characteristics and HIF-1alpha/GLUT-1 expression.
METHODS
We analyzed the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and glucose transporter-1 (GLUT-1) by immunohistochemistry in ovarian serous and mucinous tumors from the point view of the histological characteristics and acquisition of malignancy. A total of 102 ovarian tumors were examined, composed of 31 adenomas (serous 17 and mucinous 14), 32 borderline tumors (serous 13 and mucinous 19), and 39 adenocarcinomas (serous 21 and mucinous 18).


RESULTS
The overall positive ratios were as follows: HIF-1alpha, 74% of adenomas, 91% of borderline tumors, and 100% of adenocarcinomas; and GLUT-1, 68% of adenomas, 95% of borderline tumors, and 100% of adenocarcinomas. Comparing serous tumors and mucinous tumors, there was no significant difference in the positive ratios of HIF-1alpha and GLUT-1 of adenomas, borderline tumors, and adenocarcinomas. However, both markers were more strongly expressed in serous adenocarcinomas (HIF-1alpha, 3 + 100%; GLUT-1, 3+76%) than in mucinous adenocarcinomas (HIF-1alpha, 3 + 61%; GLUT-1, 3 + 28%). The results of immunoblotting and mRNA expression level analyses corresponded with those of immunohistochemical expression profiles. DNA binding assay also demonstrated that HIF-1 is more commonly activated in serous adenocarcinomas than in mucinous adenocarcinomas.


CONCLUSIONS
HIF-1alpha and GLUT-1 expressions seemed to be coordinated to adapt ovarian tumor cells into hypoxic conditions in close association with the acquisition of malignancy. We consider that the relatively strong expression of both markers in serous tumors compared with mucinous tumors is related to the difference in their histological characteristics.
Iida
Tetsuji
T
Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.
Yasuda
Masanori
M
Miyazawa
Masaki
M
Fujita
Mariko
M
Osamura
R Yoshiyuki
RY
Hirasawa
Takeshi
T
Muramatsu
Toshinari
T
Murakami
Masaru
M
Saito
Kaoru
K
Mikami
Mikio
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism
D015415:Biomarkers; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger