Correlation of HIF-1α/HIF-2α expression with FDG uptake in lung adenocarcinoma.
OBJECTIVE
Hypoxia is a key element involved in the development and progression of tumors. HIF-1α may transiently induce and mediate the response to acute and severe hypoxia, while HIF-2α may induce a longer response and may control the response to chronic and moderate hypoxia. Hypoxia increases the cellular uptake of FDG. Therefore, HIF may play an important role in the process of the cellular uptake of FDG. The aim of this study was to compare HIF-1α/HIF-2α expression with FDG uptake, Glut-1 expression, and prognosis in the patients with lung adenocarcinoma and to investigate the role of HIF-1α/HIF-2α in the uptake of FDG in lung adenocarcinoma.


METHODS
In the current work, we compared the immunohistochemical expression of HIF-1α and HIF-2α in surgical specimens of 44 patients with lung adenocarcinoma. The relationships between HIF-α expression and Glut-1 expression, FDG uptake, and clinicopathological factors, including prognosis, were analyzed.


RESULTS
There was a marginal association between HIF-1α and HIF-2α expressions (P = 0.076). We found a significant correlation between HIF-2α expression and FDG uptake (P = 0.0001). HIF-1α expression showed a marginal association with FDG uptake (P = 0.066). FDG uptake correlated more significantly with HIF-2α expression than with HIF-1α expression. A significant correlation was noticed between Glut-1 expression and both HIF-1α and HIF-2α expressions (P = 0.005 and P = 0.003, respectively). Univariate analysis of disease-free survival demonstrated that FDG uptake and HIF-2α expression, but not HIF-1α expression, were related to recurrence (P < 0.0001).


CONCLUSIONS
FDG uptake correlated more significantly with HIF-2α expression than with HIF-1α expression, and both FDG uptake and HIF-2α expression, but not HIF-1α expression was correlated with post-operative recurrence in the patients with lung adenocarcinoma. These results suggest that both FDG uptake and HIF-2α expression may represent a more aggressive phenotype and that HIF-2α may play a more important role than HIF-1α in the uptake of FDG in lung adenocarcinoma.
Department of Radiology, Asanogawa General Hospital, 83 Kosakamachi-Naka, Kanazawa, Ishikawa, 920-8621, Japan. h550208@kanazawa-med.ac.jp.
Kotaro
http://orcid.org/0000-0002-2232-7667
K
Higashi
Department of Internal Medicine, Sabae Medical Center, Sabae, Japan.
Toshiaki
T
Yamagishi
Department of Pathology, Kanazawa Medical University, Ishikawa, Japan.
Yoshimichi
Y
Ueda
Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.
Yasuhito
Y
Ishigaki
Department of Pathology, Kanazawa Medical University, Ishikawa, Japan.
Miyako
M
Shimasaki
Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.
Yuka
Y
Nakamura
Department of Radiation Therapy, Public Central Hospital of Matto Ishikawa, Ishikawa, Japan.
Manabu
M
Oguchi
Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.
Tsutomu
T
Takegami
Department of Thoracic Surgery, Kanazawa Medical University, Ishikawa, Japan.
Motoyasu
M
Sagawa
Department of Radiology, Kanazawa Medical University, Ishikawa, Japan.
Hisao
H
Tonami
D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001692:Biological Transport; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D019788:Fluorodeoxyglucose F18; D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000099162:Endothelial PAS Domain-Containing Protein 1
18F-FDG; Hypoxia-inducible factor; Lung adenocarcinoma; PET; Recurrence