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Correlation of HIF-1α/HIF-2α expression with FDG uptake in lung adenocarcinoma

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Abstract

Objectives

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).

Conclusion

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.

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Acknowledgments

This study was partially supported by a grant-in-aid for scientific research (26460442) to YU from the Ministry of Education, Science, and Culture, Japan and a grant for specially promoted research from Kanazawa Medical University (SR2012-01) to YU.

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Authors and Affiliations

  1. Department of Radiology, Asanogawa General Hospital, 83 Kosakamachi-Naka, Kanazawa, Ishikawa, 920-8621, Japan

    Kotaro Higashi

  2. Department of Internal Medicine, Sabae Medical Center, Sabae, Japan

    Toshiaki Yamagishi

  3. Department of Pathology, Kanazawa Medical University, Ishikawa, Japan

    Yoshimichi Ueda & Miyako Shimasaki

  4. Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan

    Yasuhito Ishigaki, Yuka Nakamura & Tsutomu Takegami

  5. Department of Radiation Therapy, Public Central Hospital of Matto Ishikawa, Ishikawa, Japan

    Manabu Oguchi

  6. Department of Thoracic Surgery, Kanazawa Medical University, Ishikawa, Japan

    Motoyasu Sagawa

  7. Department of Radiology, Kanazawa Medical University, Ishikawa, Japan

    Hisao Tonami

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  1. Kotaro Higashi
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  2. Toshiaki Yamagishi
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  3. Yoshimichi Ueda
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Correspondence to Kotaro Higashi.

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Higashi, K., Yamagishi, T., Ueda, Y. et al. Correlation of HIF-1α/HIF-2α expression with FDG uptake in lung adenocarcinoma. Ann Nucl Med 30, 708–715 (2016). https://doi.org/10.1007/s12149-016-1116-5

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  • DOI: https://doi.org/10.1007/s12149-016-1116-5

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