Changes in mast cell number and stem cell factor expression in human skin after radiotherapy for breast cancer

Abstract

Background and purposeMast 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. Materials and methodsPunch biopsies of skin 1 and 15–18months 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 18months and 5years 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. ResultsDermal mast cell numbers were increased at 1 (p=0.047) and 18months (p=0.040) using c-Kit, and at 18months (p=0.024) using tryptase immunostaining. Collagen-1 mRNA in skin was increased at 1month (p=0.047) and 18months (p=0.032) and SCF mRNA increased at 1month (p=0.003). None of 16 cases scored had a change in photographic appearance at 5years, compared to baseline. SCF expression was not increased in HDMECs irradiated in vitro. ConclusionsIncreased 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 1month 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 18months after radiotherapy in breast cancer patients with no change in photographic breast appearance at 5years.