title: Changes in mast cell number and stem cell factor expression in human skin after radiotherapy for breast cancer.
abstract: OBJECTIVE
  Mast cells are involved in the pathogenesis of radiation fibrosis and may be a therapeutic target. The mechanism of increased mast cell number in relation to acute and late tissue responses in human skin was investigated.
  
  
  METHODS
  Punch biopsies of skin 1 and 15-18 months after breast radiotherapy and a contralateral control biopsy were collected. Mast cells were quantified by immunohistochemistry using the markers c-Kit and tryptase. Stem cell factor (SCF) and collagen-1 expression was analysed by qRT-PCR. Clinical photographic scores were performed at post-surgical baseline and 18 months and 5 years post-radiotherapy. Primary human dermal microvascular endothelial cell (HDMEC) cultures were exposed to 2Gy ionising radiation and p53 and SCF expression was analysed by Western blotting and ELISA.
  
  
  RESULTS
  Dermal mast cell numbers were increased at 1 (p=0.047) and 18 months (p=0.040) using c-Kit, and at 18 months (p=0.024) using tryptase immunostaining. Collagen-1 mRNA in skin was increased at 1 month (p=0.047) and 18 months (p=0.032) and SCF mRNA increased at 1 month (p=0.003). None of 16 cases scored had a change in photographic appearance at 5 years, compared to baseline. SCF expression was not increased in HDMECs irradiated in vitro.
  
  
  CONCLUSIONS
  Increased mast cell number was associated with up-regulated collagen-1 expression in human skin at early and late time points. This increase could be secondary to elevated SCF expression at 1 month after radiotherapy. Although mast cells accumulate around blood vessels, no endothelial cell secretion of SCF was seen after in vitro irradiation. Modification of mast cell number and collagen-1 expression may be observed in skin at 1 and 18 months after radiotherapy in breast cancer patients with no change in photographic breast appearance at 5 years.
authors.affiliation: Department of Oncology, UCL Cancer Institute, University College London, United Kingdom; Department of Oncology, Hillingdon Hospital, Uxbridge, United Kingdom; Mount Vernon Cancer Centre, Middlesex, United Kingdom. Electronic address: charlotte.westbury@thh.nhs.uk.
authors.forename: Charlotte B
authors.initials: CB
authors.lastname: Westbury
authors.affiliation: Department of Histopathology, University College London Hospitals NHS Trust, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: Freeman
authors.affiliation: Department of Oncology, UCL Cancer Institute, University College London, United Kingdom.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Rashid
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom.
authors.forename: Ann
authors.initials: A
authors.lastname: Pearson
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom.
authors.forename: John R
authors.initials: JR
authors.lastname: Yarnold
authors.affiliation: Department of Oncology, UCL Cancer Institute, University College London, United Kingdom; Leeds Institute of Cancer and Pathology, University of Leeds, United Kingdom.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Short
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D002452:Cell Count; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000528:radiation effects; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008137:Longitudinal Studies; D008297:Male; D008407:Mast Cells; D008875:Middle Aged; D011446:Prospective Studies; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011832:Radiation Injuries / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D024042:Collagen Type I; D012333:RNA, Messenger; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit
keywords: Mast cell; Photographic breast appearance; Radiation fibrosis; Stem cell factor