Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients.
Hypoxia within head and neck squamous cell carcinoma (HNSCC) predicts a poor response to radiotherapy and poor prognosis. Hypoxia-inducible factor (HIF)-1 and HIF-2 are nuclear transcription factors that regulate the cellular response to hypoxia and are important for solid tumor growth and survival. Overexpression of HIF-1alpha and HIF-2alpha was demonstrated in three HNSCC cell lines under hypoxia and tumor tissue versus normal tissue (n = 20, HIF-1alpha, P = 0.023; HIF-2alpha, P = 0.013). On immunostaining, HIF-1alpha and HIF-2alpha expression were localized to tumor nuclei; HIF-2alpha expression was also seen in tumor-associated macrophages. Expression of HIF-1alpha in surgically treated patients with HNSCC (n = 79) was associated with improved disease-free survival (P = 0.016) and overall survival (P = 0.027).
Beasley
Nigel J P
NJ
Oxford Centre for Head and Neck Oncology, Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom.
Leek
Russell
R
Alam
Mohammed
M
Turley
Helen
H
Cox
Graham J
GJ
Gatter
Kevin
K
Millard
Peter
P
Fuggle
Sue
S
Harris
Adrian L
AL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D006367:HeLa Cells; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008875:Middle Aged; D009336:Necrosis; D015996:Survival Rate; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis*; D016896:Treatment Outcome; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007770:L-Lactate Dehydrogenase; D015534:Trans-Activators; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human