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10.1245/s10434-008-9955-5
Annals of Surgical Oncology 15:2336-2344 (2008)
© 2008 Society of Surgical Oncology
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Original Article

Lactate Dehydrogenase-5 (LDH-5) Expression in Human Gastric Cancer: Association with Hypoxia-Inducible Factor (HIF-1{alpha}) Pathway, Angiogenic Factors Production and Poor Prognosis

Yanislav Kolev, MD, PhD, Hiroyuki Uetake, MD, PhD, Yoko Takagi and Kenichi Sugihara, MD, PhD

Surgical Oncology Department, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan

Correspondence: Address correspondence and reprint requests to: Yanislav Kolev, MD, PhD; E-mail: kolev.srg2{at}tmd.ac.jp; yanislavkolev{at}yahoo.com

Background: Lactate-dehydrogenase-5 (LDH-5) is an important isoenzyme converting pyruvate to lactate under hypoxic conditions and might play an important role in the development and progression of malignancies. However, the role of LDH-5 in gastric cancer is still unclear. In this study, we investigated the clinical significance of LDH-5 expression in gastric carcinoma.

Methods: LDH-5 expression in 152 patients with different grade and stage gastric carcinoma was analyzed by immunohistochemistry. In addition, hypoxia-inducible factor 1{alpha} (HIF-1{alpha}) as a marker of tumor hypoxia, as well as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) as angiogenesis parameters were also assessed in this study. Correlations between the expression of investigated proteins and various clinicopathological factors including survival were determined.

Results: There were 94 cases (61.8%) showing high LDH-5 expression, and 95 patients (62.5%) had high HIF-1{alpha} expression. Positive correlation was found between LDH-5 expression and HIF-1{alpha}, VEGF, and COX-2. The overexpression of LDH-5 was more prevalent in advanced tumors having positive vessel invasion. Patients with overexpression of LDH-5 showed far lower disease-free (63.5% vs 82.7%) and overall (56.3% vs 78.4%) survival rates compared with patients with low LDH-5 expression. HIF-1{alpha} expression was shown to have no significance on survival. In multivariate analysis, high LDH-5 expression kept its independence as a negative prognostic indicator.

Conclusion: The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.

Key Words: LDH-5 • HIF-1 • Prognosis • Gastric cancer




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