title: Expression of hypoxia-inducible factor-1α, vascular endothelial growth factor and prolyl hydroxylase domain protein 2 in cutaneous squamous cell carcinoma and precursor lesions and their relationship with histological stages and clinical features.
abstract: The hypoxia-inducible factor-1 (HIF-1α) pathway is associated with tumor growth, angiogenesis and metastasis in various carcinomas. Little is known regarding the role of the HIF-1α signaling pathway in cutaneous squamous cell carcinoma (SCC). We investigated the expression of HIF-1α, vascular endothelial growth factor (VEGF) and the HIF negative regulator, prolyl hydroxylase domain protein 2 (PHD2), in cutaneous SCC, Bowen's disease, seborrheic keratosis (SK) and normal skin by immunohistochemistry and in situ hybridization. Additionally, we explored the relationships between these factors and the clinical and histological characteristics of each disease. Our study indicated that the expression of HIF-1α and VEGF was significantly higher (P < 0.05) in cutaneous SCC than in Bowen's disease, SK or normal skin. In contrast, PHD2 showed significantly higher expression in normal skin compared with SK, Bowen's disease and cutaneous SCC (P < 0.05). Grade II-IV cutaneous SCC had higher expression levels of nuclear HIF-1α and cytoplasm VEGF protein but less nuclear PHD2 protein than grade Ι cutaneous SCC (P < 0.05). Overexpression of HIF-1α and VEGF, as well as the decreased expression of PHD2, may play important roles in the development of cutaneous SCC.
authors.affiliation: Department of Dermatology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiangjie
authors.initials: X
authors.lastname: An
authors.forename: Guangfen
authors.initials: G
authors.lastname: Xu
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Yuejue
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Uwesu O
authors.initials: UO
authors.lastname: McHepange
authors.forename: Guanxin
authors.initials: G
authors.lastname: Shen
authors.forename: Yating
authors.initials: Y
authors.lastname: Tu
authors.forename: Juan
authors.initials: J
authors.lastname: Tao
mesh_terms: D001913:Bowen's Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000150:complications; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000378:metabolism*; D017492:Keratosis, Seborrheic / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C490190:EGLN1 protein, human; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases
keywords: cutaneous squamous cell carcinoma; hypoxia-inducible factor-1α; prolyl hydroxylases 2; vascular endothelial growth factor