title: An expression analysis of markers of radiation-induced skin fibrosis and angiogenesis in wound healing disorders of the head and neck.
abstract: BACKGROUND
  Radiation-induced fibrosis (RIF) is one of the severe long-term side effects of radiation therapy (RT) with a crucial impact on the development of postoperative wound healing disorders (WHD). The grades of fibrosis vary between mild to severe depending on individual radiosensitivity. In this study, we have investigated the molecular pathways that influence RIF and have correlated data from immunohistochemistry (IHC) for von -Willebrand Factor (vWF) and from Real-Time Polymerase Chain Reaction (RT-PCR) concerning markers such as Transforming Growth Factor (TGF)-β 1, and vWF, with clinical data concerning the occurrence of WHD during follow-up.
  
  
  METHODS
  Expression profiles of the genes encoding TGF-β 1, vWF, and α-procollagen (PC) were analyzed, by RT-PCR, in specimens from patients with (n = 20; 25.6 %) and without (n = 58; 74.4 %) a history of previous RT to the head and neck. Moreover, IHC against vWF was performed. Clinical data on the occurrence of cervical WHDs were analyzed and correlated.
  
  
  RESULTS
  A statistically significant increase in the expression profiles of α-PC and TGF-β 1 was observed in previously irradiated skin samples (occurrence of RT >91 days preoperatively). vWF showed a statistically significant increase in non-irradiated tissue. Moreover, analysis of expression profiles in patients with and without WHDs during follow-up was performed. IHC showed a reduced amount of vessels and structural changes in epidermal tissue post-RT.
  
  
  CONCLUSIONS
  The expression of markers of fibrosis and angiogenesis was analyzed in order to gain insight into molecular pathways that account for structural changes in irradiated skin and that eventually lead to WHDs. The results are congruent with reports from the literature and are a possible starting point for further research, as anti-TGF-β 1 treatment, for example, could represent new therapeutic opportunities in the management of previously irradiated patients.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. steffen.koerdt@tum.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Koerdt
authors.affiliation: Department of Oral and Maxillofacial Surgery, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. nils.rohleder@tum.de.
authors.forename: Nils H
authors.initials: NH
authors.lastname: Rohleder
authors.affiliation: Department of Oral and Maxillofacial Surgery, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. niklas.rommel@tum.de.
authors.forename: Niklas
authors.initials: N
authors.lastname: Rommel
authors.affiliation: Department of Oral and Maxillofacial Surgery, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. Christopher_nobis@hotmail.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Nobis
authors.affiliation: Department of Oral and Maxillofacial Surgery, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. mechthild.stoeckelhuber@tum.de.
authors.forename: Mechthild
authors.initials: M
authors.lastname: Stoeckelhuber
authors.affiliation: Department of Radiation Oncology, Technische Universität München, Ismaninger Str.22, 81675, Munich, Germany. Steffi.pigorsch@lrz.tu-muenchen.de.
authors.forename: Steffi
authors.initials: S
authors.lastname: Pigorsch
authors.affiliation: Department of Radiation Oncology, Technische Universität München, Ismaninger Str.22, 81675, Munich, Germany. marciana.duma@mri.tum.de.
authors.forename: Marciana-Nona
authors.initials: MN
authors.lastname: Duma
authors.affiliation: Department of Oral and Maxillofacial Surgery, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. klaus-dietrich.wolff@tum.de.
authors.forename: Klaus-Dietrich
authors.initials: KD
authors.lastname: Wolff
authors.affiliation: Department of Oral and Maxillofacial Surgery, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. marco.kesting@tum.de.
authors.forename: Marco R
authors.initials: MR
authors.lastname: Kesting
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D005260:Female; D005355:Fibrosis / Q000209:etiology; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology; D011832:Radiation Injuries / Q000378:metabolism* / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000528:radiation effects; D059467:Transcriptome; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000096:biosynthesis; D014945:Wound Healing / Q000502:physiology*; D014841:von Willebrand Factor / Q000032:analysis / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; D053773:Transforming Growth Factor beta1; D014841:von Willebrand Factor