Clinicopathologic significance of hypoxia-inducible factor 1α overexpression in gastric carcinomas

Ken Mizokami, Yoshihiro Kakeji, Shinya Oda, Koji Irie, Tomohiro Yonemura, Fumio Konishi, Yoshihiko Maehara

Research output: Contribution to journalArticle

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Abstract

Background: Hypoxia-inducible factor 1α (HIF-1α) plays a key role in responses to hypoxia and expression of HIF-1α downstream genes leads to both an adapted metabolism and increased oxygen supply. We investigated the clinical significance of HIF-1α expression in gastric carcinoma. Methods: We examined HIF-1α, vascular endothelial growth factor (VEGF), and insulin-like growth factor-2 (IGF-2) expression patterns immunohistochemically in 126 specimens of gastric carcinoma. CD34 antigen levels were also examined by immunohistochemistry to determine microvessel density (MVD) within tumors and correlations between HIF-1α expression, clinicopathological features, and survival were examined. Results: HIF-1α expression correlated with tumor size (P < 0.005), depth of invasion (P = 0.018), VEGF expression (P = 0.03), and intra-tumor MVD (P < 0.005). IGF-2 expression was more prevalent in HIF-1α positive than in HIF-1α negative tumors and the 5-year survival rate was 58.4% for HIF-1α positive patients and 81.5% for HIF-1α negative patients (P = 0.009). HIF-1α expression is an independent prognostic factor in gastric carcinoma (P = 0.032). Conclusions: Overexpression of HIF-1α in gastric carcinomas may upregulate its downstream gene products leading to VEGF-mediated angiogenesis, and resulting in a poor prognosis for patients.

Original languageEnglish
Pages (from-to)149-154
Number of pages6
JournalJournal of Surgical Oncology
Volume94
Issue number2
DOIs
Publication statusPublished - Aug 1 2006

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Hypoxia-Inducible Factor 1
Stomach
Carcinoma
Vascular Endothelial Growth Factor A
Somatomedins
Microvessels
Neoplasms
CD34 Antigens
Genes
Up-Regulation
Survival Rate

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Mizokami, K., Kakeji, Y., Oda, S., Irie, K., Yonemura, T., Konishi, F., & Maehara, Y. (2006). Clinicopathologic significance of hypoxia-inducible factor 1α overexpression in gastric carcinomas. Journal of Surgical Oncology, 94(2), 149-154. https://doi.org/10.1002/jso.20568

Clinicopathologic significance of hypoxia-inducible factor 1α overexpression in gastric carcinomas. / Mizokami, Ken; Kakeji, Yoshihiro; Oda, Shinya; Irie, Koji; Yonemura, Tomohiro; Konishi, Fumio; Maehara, Yoshihiko.

In: Journal of Surgical Oncology, Vol. 94, No. 2, 01.08.2006, p. 149-154.

Research output: Contribution to journalArticle

Mizokami, K, Kakeji, Y, Oda, S, Irie, K, Yonemura, T, Konishi, F & Maehara, Y 2006, 'Clinicopathologic significance of hypoxia-inducible factor 1α overexpression in gastric carcinomas', Journal of Surgical Oncology, vol. 94, no. 2, pp. 149-154. https://doi.org/10.1002/jso.20568
Mizokami, Ken ; Kakeji, Yoshihiro ; Oda, Shinya ; Irie, Koji ; Yonemura, Tomohiro ; Konishi, Fumio ; Maehara, Yoshihiko. / Clinicopathologic significance of hypoxia-inducible factor 1α overexpression in gastric carcinomas. In: Journal of Surgical Oncology. 2006 ; Vol. 94, No. 2. pp. 149-154.
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