Expression of hypoxia inducible factor-1alpha (HIF-1alpha) and glucose transporter-1 (GLUT-1) in ovarian adenocarcinomas: difference in hypoxic status depending on histological character.
The expression of hypoxia inducible factor-1alpha (HIF-1alpha) and glucose transporter-1 (GLUT-1) was immunohistochemically analyzed in ovarian adenocarcinomas with the aim of elucidating whether hypoxic status is associated with histological type or structural character. The following ovarian adenocarcinomas were used: serous adenocarcinoma (SEA), 21 cases; mucinous adenocarcinoma (MUA), 19 cases; endometrioid adenocarcinoma (ENA), 16 cases; clear cell adenocarcinoma (CLA), 19 cases. High-level expression (3+) of HIF-1alpha was observed in 100% of SEAs, 58% of MUAs, 100% of ENAs and 89% of CLAs, and high-level expression of GLUT-1 in 76% of SEAs, 26% of MUAs, 50% of ENAs and 67% of CLAs. Heterogeneous or localized staining was relatively evident for GLUT-1. Immunohistochemical profiles were in accord with the immunoblotting and mRNA levels of both markers. ELISA for the detection of active HIF-1 demonstrated that HIF-1 is strongly activated in SEAs, ENAs and CLAs as compared to MUAs. Our results show that GLUT-1 overexpression is to some extent regulated by HIF-1alpha and is also strongly associated with histological features, i.e., papillary or stratified structure accompanied by little or no vascular stroma. In conclusion, hypoxic status differs according to the histological type of ovarian adenocarcinoma and the micro-environmental conditions of each type.
Yasuda
Masanori
M
Department of Pathology, Saitama Medical University International Medical Center, Saitama 350-1298, Japan. m_yasuda@saitama-med.ac.jp
Miyazawa
Masaki
M
Fujita
Mariko
M
Kajiwara
Hiroshi
H
Iida
Tetsuji
T
Hirasawa
Takeshi
T
Muramatsu
Toshinari
T
Murakami
Masaru
M
Mikami
Mikio
M
Saitoh
Kaoru
K
Shimizu
Michio
M
Takekoshi
Susumu
S
Osamura
R Yoshiyuki
RY
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis*; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D027342:Excitatory Amino Acid Transporter 2; D012333:RNA, Messenger; D000099162:Endothelial PAS Domain-Containing Protein 1