Radiotherapy-induced basal cell carcinomas of the scalp: Are they genetically different?

Background: The treatment of tinea capitis using radiotherapy was introduced at the beginning of the twentieth century. In Israel, between 1949 and 1960, approximately 17,000 children underwent radiotherapy treatments for tinea capitis (actual numbers are probably higher due to irradiation in countries of origin as a prerequisite for immigration). Skin cancer presents a major problem for patients who underwent irradiation for the treatment of tinea capitis [aggressive biological behavior, multiple basal cell carcinomas (BCCs), up to 40 lesions in a single patient, with no predisposing condition such as Gorlin's or Bazex's syndromes]. There are ample data in the literature concerning the molecular changes in ultraviolet (UV) radiation-induced BCCs. However, similar data regarding ionizing radiation-induced BCCs are scarce. One work found higher rates of p53 and PTCH (both are tumor suppressor genes whose alterations are associated with BCC formation and frequency, but not biological behavior) abnormalities in post ionizing radiation BCCs. The absence of documented differences in gene expression that would account for a different biological behavior of radiotherapy-related BCCs, coupled with the aggressive and recurrent nature of these lesions, has propelled us to examine these differences by comparing gene expression in BCCs of the scalps of patients who were previously irradiated for tinea capitis in their childhood and of the scalps of patients who were not. Methods: Tissue samples of excised scalp BCCs from seven previously irradiated patients (five male, two female) and seven not previously irradiated patients (six male, one female) were frozen upon excision and genetically analyzed using DNA microarray chips. Results: No correlation was found between previous ionizing irradiation and gene expression. Conclusions: The negative results of this study, coupled with the observation of aggressive biological behavior of BCCs in previously irradiated patients merit further attention. Other explanations for the aggressive biological behavior of radiotherapy-induced BCCs come to mind. One such explanation could be that the difference between the groups lies not in the tumor itself, but in the host, who is more susceptible to the local destruction caused by the tumor due to changes in the surrounding tissue (e.g., impaired blood supply due to radiation, structural damage in seemingly healthy skin). This hypothesis will be the focus of further research. Level of Evidence II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.