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Overexpression of Hypoxia Inducible Factor-1 Alpha is an Independent Risk Factor for Recurrence After Curative Resection of Colorectal Liver Metastases

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Hypoxia inducible factor-1α (HIF-1α) is a major regulator of tumorigenesis in hypoxic conditions and therefore represents a potential therapeutic target in colorectal cancer (CRC). Clinical significance of HIF-1α expression in liver metastases has not been elucidated. Therefore, this study aimed to clarify the clinical significance of HIF-1α expression in colorectal liver metastasis (CRLM).

Methods

We retrospectively analyzed 64 patients who underwent curative resection of CRLM from 2000 to 2008. We evaluated HIF-1α expression by immunohistochemical staining and analyzed its association with several clinicopathological characteristics, including vascular endothelial growth factor (VEGF) expression. We analyzed the mutation status of genes involved in CRC (p53, KRAS, BRAF, and PIK3CA). Finally, we compared HIF-1α expression between the primary tumor and the corresponding liver metastases.

Results

We found a significant positive correlation between HIF-1α expression in liver metastases and PIK3CA mutation status (p = 0.019). A significant correlation was also observed between the expressions of HIF-1α and VEGF in liver metastases and primary tumors (p = 0.015, 0.024, respectively). High HIF-1α expression in liver metastases was an independent risk factor for recurrence (p = 0.031).

Conclusions

Our results suggest a possible induction of HIF-1α expression by mutant PIK3CA. The expressions of HIF-1α and VEGF in liver metastases significantly correlated with those in the corresponding primary tumor. Overexpression of HIF-1α was an independent risk factor for recurrence after curative resection of CRLM, suggesting that HIF-1α represents an important candidate for the treatment of CRLM in a subset of patients with high HIF-1α expression.

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Acknowledgment

We thank Yuko Ishida and Midori Kiyokawa for their expert technical assistance, and the Analysis Center of Life Science, Hiroshima University, for the use of their facilities.

Disclosure

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Manabu Shimomura MD, Takao Hinoi MD, Shintaro Kuroda MD, Tomohiro Adachi MD, Yasuo Kawaguchi MD, Tatsunari Sasada MD, Yuji Takakura MD, Hiroyuki Egi MD, Masazumi Okajima MD, Hirotaka Tashiro MD & Hideki Ohdan MD

  2. Department of Pathology, Hiroshima Prefectural Hospital, Hiroshima, Japan

    Takashi Nishizaka MD

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  1. Manabu Shimomura MD
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  2. Takao Hinoi MD
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Correspondence to Takao Hinoi MD.

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Shimomura, M., Hinoi, T., Kuroda, S. et al. Overexpression of Hypoxia Inducible Factor-1 Alpha is an Independent Risk Factor for Recurrence After Curative Resection of Colorectal Liver Metastases. Ann Surg Oncol 20 (Suppl 3), 527–536 (2013). https://doi.org/10.1245/s10434-013-2945-2

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  • DOI: https://doi.org/10.1245/s10434-013-2945-2

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