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JPTM > Volume 44(4); 2010 > Article
The Korean Journal of Pathology 2010;44(4): 360-369.
doi: https://doi.org/10.4132/KoreanJPathol.2010.44.4.360
Prognostic Significance of Glycolytic Metabolic Change Related to HIF-1alpha in Oral Squamous Cell Carcinomas.
Sook Hee Hong, Sang Young Roh, Yoon Ho Ko, Hye Sung Won, Myung Ah Lee, In Sook Woo, Jae Ho Byun, Jin Hyoung Kang, Young Seon Hong, Chan Kwon Jung, Yeon Sil Kim, Young Hoon Ju, Min Sik Kim
1Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
2Department of Pathology, The Catholic University of Korea College of Medicine, Seoul, Korea. ssuki76@catholic.ac.kr
3Department of Radiation Oncology, The Catholic University of Korea College of Medicine, Seoul, Korea.
4Department of Otorhinolaryngology, The Catholic University of Korea College of Medicine, Seoul, Korea.
ABSTRACT
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)-1alpha and prognosis. METHODS: We performed immunohistochemical staining of HIF-1alpha, 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-1alpha, 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-1alpha may be independent prognostic factors in patients with oral SCC.
Key Words: Carcinoma, squamous cell; HIF1A protein, human; Lactate dehydrogenase 5; Pyruvate dehydrogenase (acetyl-transferring) kinase