Background

Mast cells are implicated in radiation fibrosis, and may be a potential therapeutic target. The interaction of stem cell factor (SCF) with its receptor c-Kit, expressed on mast cells, is important for their recruitment and activation, but the relevance to radiation fibrosis is unknown. We investigated mast cell numbers in human skin from patients who had radiotherapy for early breast cancer and SCF expression in tissue and in an in vitro radiation model.

Method

Paired punch biopsies of skin were obtained from the contralateral breast (control) and from within the irradiated field of the treated breast, one month after the start and 18 months after completion of radiotherapy. Duplicate samples were formalin fixed and paraffin embedded for immunohistochemistry or snap frozen in liquid nitrogen for molecular analysis. Immunostaining was performed with antibodies against the mast cell markers c-Kit and tryptase, and for each marker, the number of immune-positive cells was scored. Statistical analysis was performed using the Wilcoxon signed-rank test.

Results

Tissue was included from 14 patients. Average mast cell number for control, one month and 18 months scored using c-Kit immunostaining was 3.7±0.4, 5.2±0.7 (control vs one month p=0.047), and 5.3±0.8 (control vs 18 months p=0.040) and using tryptase was 6.0±0.6, 6.7±0.4 (control vs one month p=0.136) and 8.1±0.7 (control vs 18 months p=0.024), respectively.

Conclusion

Mast cell numbers were increased in irradiated human skin from patients who previously received radiotherapy for breast cancer. This increase was seen at both one and 18 months after completion of the treatment course. These data provide indirect evidence for the role of mast cells in chronic injury in human skin after radiation. The investigation of SCF expression, its regulating factors and pro-fibrotic markers in these tissue samples and in an in vitro model of endothelial cell irradiation is underway.