title: Analysis of angiogenic markers in oral squamous cell carcinoma-gene and protein expression.
abstract: OBJECTIVE
  Therapeutic strategies attacking oral squamous cell carcinoma have not essentially succeeded to improve long-term prognosis and overall survival over the last decades. Therefore, in this study, we aimed to illuminate the molecular regulation of angiogenesis in this tumour entity in order to demask novel markers of prognosis or therapeutic approach.
  
  
  METHODS
  A panel of significant transcriptional alterations in angiogenic genes of 83 cancer samples was established by comparison to 30 samples of healthy oral mucosa with microarray technique. Immunohistochemistry (IHC) was performed to trace the signalling cascade from gene to protein level.
  
  
  RESULTS
  A distinctive expression profile of VEGFA, EFNB2, PECAM1/CD31, ANGPT1 and ANGPT2 was revealed: VEGFA, EFNB2, and ANGPT2 were found overexpressed in 84 % to 95 % of tumour samples. In contrast, the expression of CD31 and ANGPT1 was downregulated in 80 % to 95 % of tumour samples. IHC confirmed results of the microarray analysis. Tumours with lymphatic spread showed higher gene expression rates of VEGFA, EFNB2 and ANGPT2 in moderately differentiated tumours and of VEGFA and EFNB2 in small tumours, respectively. The ANGPT1/ ANGPT2 transcription ratio was found decreased in larger tumours and especially in tumours without lymphatic spread.
  
  
  CONCLUSIONS
  A characteristic expression profile of angiogenic markers was established. The specific overexpression of EFNB2 in small tumours with lymphatic spread and the typical decrease of the ANGPT1/ ANGPT2 ratio in larger tumours give weight to EFNB2 and angiopoietins as prognostic factors and potential therapeutic targets.
authors.affiliation: Vascular Biology of Oral Structures (VABOS) Research Unit, Department of Cranio-Maxillofacial Surgery, University Hospital Muenster, Waldeyerstraße 30, D-48149, Muenster, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Jung
authors.affiliation: Vascular Biology of Oral Structures (VABOS) Research Unit, Department of Cranio-Maxillofacial Surgery, University Hospital Muenster, Waldeyerstraße 30, D-48149, Muenster, Germany. Sonja.Sielker@ukmuenster.de.
authors.forename: Sonja
authors.initials: S
authors.lastname: Sielker
authors.affiliation: Department of Cranio-Maxillofacial Surgery, University Hospital Kiel, Kiel, Germany.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Purcz
authors.affiliation: Department of Cranio-Maxillofacial Surgery, University Hospital Duesseldorf, Duesseldorf, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sproll
authors.affiliation: Department of Cranio-Maxillofacial Surgery, University Hospital Kiel, Kiel, Germany.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Acil
authors.affiliation: Vascular Biology of Oral Structures (VABOS) Research Unit, Department of Cranio-Maxillofacial Surgery, University Hospital Muenster, Waldeyerstraße 30, D-48149, Muenster, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kleinheinz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000235:genetics*; D042702:Angiopoietin-2 / Q000235:genetics*; D001707:Biopsy, Needle; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2