An immunohistochemical analysis of radiation fibroblasts

A commonly recognized feature of chronic radiation dermatitis is the presence of mesenchymal cells with large atypical nuclei known as radiation fibroblasts. Little is known about their lineage or potential for neoplastic transformation. To investigate these properties, we examined 16 biopsy specimens in which radiation fibroblasts were present with antisera to mesenchymal determinants (FXIIIa, CD34, HHF-35), a proliferation marker (Ki-67), and a tumor-suppressor protein that is overexpressed in many cancers (p53). Radiation fibroblasts were largely negative for the markers of lineage that we employed - only 2 of 16 specimens showed strong expression of FXIIIa, with weak expression in another case. Scattered radiation fibroblasts expressed CD34 in one case. HHF-35 (muscle specific actin) stained small, dendritic cells in the superficial dermis, but not radiation fibroblasts. P53 was not detected within radiation fibroblasts in any of our cases, but was overexpressed by endothelial cells in 2 cases. Ki-67 stained rare endothelial and interstitial cells but not radiation fibroblasts. Radiation fibroblasts are immunophenotypically distinct from dermal dendrocytes and myofibroblasts. They appear to be non-cycling cells, and do not express high levels of p53 despite their marked nuclear atypia. Their phenotype argues against their possible role as progenitors of atypical fibroxanthoma (AFX) and dermatofibrosarcoma protuberans (DFSP) which are associated with ionizing radiation-induced skin damage.