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KMID : 0357920100440040360
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Korean Journal of Pathology
2010 Volume.44 No. 4 p.360 ~ p.369
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Prognostic Significance of Glycolytic Metabolic Change Related to HIF-1α in Oral Squamous Cell Carcinomas
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Hong Sook-Hyee
Roh Sang-Young
Ko Yoon-Ho
Won Hye-Sung
Lee Myung-Ah
Woo In-Sook
Byeon Jae-Ho
Kang Jin-Hyoung
Hong Young-Seon
Jung Chan-Kwon
Kim Yeon-Sil
Joo Young-Hoon
Kim Min-Sik
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Abstract
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Background: Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to aggressive behavior. We investigated the relationship between glycolytic metabolism biomarkers associated with hypoxia-inducible factor (HIF)-1α and prognosis.
Methods: We performed immunohistochemical staining of HIF-1α, pyruvate dehydrogenase kinase (PDK) 1 and lactate dehydrogenase (LDH) 5 in 74 patients with oral squamous cell carcinoma (SCC) who had received curative radical resection.
Results: High reactivity of HIF-1α, PDK 1 and LDH 5 was observed in 29 (39.2%), 32 (43.2%) and 54 (73.0%) patients, respectively. Expression levels of the three biomarkers were significantly correlated. All three markers were highly expressed in 16 (21.6%) patients. Elevated expression of the three markers was associated with increased invasiveness (p = 0.043) and recurrence (p = 0.017) of tumors. In survival analysis, upregulation of the three markers was additionally associated with shorter disease free survival (DFS, p = 0.001) and overall survival (OS, p = 0.002). High expression of all three markers was a strong independent prognostic factor for DFS (p = 0.030) and OS (p = 0.026).
Conclusions: Oral SCC with altered glycolytic metabolism exhibits a more invasive and aggressive phenotype. Our results indicate that glycolytic metabolism biomarkers related to HIF-1α may be independent prognostic factors in patients with oral SCC.
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KEYWORD
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Carcinoma, squamous cell, HIF1A protein, human, Lactate dehydrogenase 5, Pyruvate dehydrogenase (acetyl-transferring) kinase
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