title: Immunohistochemical study of VEGF expression in oral squamous cell carcinomas: correlation with the mTOR-HIF-1α pathway.
abstract: The aim of this study was to clarify the relationship between vascular endothelial growth factor (VEGF) expression and clinicopathological factors in oral squamous cell carcinoma (OSCC). We also examined the correlation between the VEGF expression and the mammalian target of rapamycin (mTOR)-hypoxia inducible factor-1α (HIF-1α) pathway. Formalin-fixed paraffin-embedded tissues from 120 OSCC cases and 10 samples of normal mucosa were stained immunohistochemically for VEGF-A, VEGF-C, p-mTOR and HIF-1α proteins. VEGF-A and VEGF-C protein expression was detected in 76 out of 120 (63%) and 81 of 120 (67.5%) OSCCs, respectively, and their expression was significantly higher in primary OSCC than in normal oral mucosa. VEGF-A expression was significantly associated with the tumor stage and age. VEGF-C expression was significantly associated with the cancer cell invasion. The cases with combined p-mTOR+/HIF-1α(+)/VEGF-A(+) expression had a significantly higher tumor stage and invasion grade, and combined p-mTOR+/HIF-1α(+)/VEGF-C(+) expression was significantly associated with tumor stage, regional lymph node metastasis and invasion grade. In a survival analysis, no obvious correlation was observed with any of the immunohistochemical results. This study indicated that the mTOR-HIF-1α-VEGF pathway affects the progression of OSCC, and inhibition of this pathway may be useful for the treatment of OSCC.
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, Nagasaki, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Naruse
authors.forename: Goro
authors.initials: G
authors.lastname: Kawasaki
authors.forename: Souichi
authors.initials: S
authors.lastname: Yanamoto
authors.forename: Akio
authors.initials: A
authors.lastname: Mizuno
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umeda
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D016022:Case-Control Studies; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry / Q000379:methods*; D008207:Lymphatic Metastasis; D009062:Mouth Neoplasms / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases