Expression of p53 in arsenic-related and sporadic basal cell carcinoma

Background: The TP53 gene has been shown to have an important role in the g enesis of sporadic, presumably mainly sunlight-related, basal cell carcinom a (BCC). However, its role in arsenic-related BCCs is not clear, although t he trivalent form of arsenic has been long recognized as a cause of BCC. Ar senic treatment has been shown to cause hypermethylation of the TP53 gene i n lung carcinoma cell lines, but it is not known if this occurs in vivo in arsenic-related BCCs. Objective: To compare the immunohistochemical expression of the p53 protein in arsenic-related and sporadic BCCs to determine if the expression patter n is consistent with gene silencing. Setting: A research institute and hospital in Australia. Cases: One hundred seventeen white patients with 121 sporadic BCCs and 21 w hite patients with 92 arsenic-related BCCs. Main Outcome Measures: The expression and the in-tensity of p53 were scored semiquantitatively. Statistical analysis was performed using the chi(2) te st. Results: Arsenic-related BCCs express p53 less often and at a lower intensi ty than sporadic BCCs (P = .001; 2-tailed test). The BCCs from sun-exposed sites, whether arsenic related or sporadic, more frequently showed overexpr ession of p53 than those from less-exposed areas (P = .004, 2-tailed test). The more aggressive subtypes of BCC show a higher level of expression of p 53 than the less aggressive forms (P = .04; 2-tailed chi(2) test). Conclusions: These results are consistent with the hypothesis that the TP53 gene is down-regulated by methylation in arsenic-related BCC, particularly those from less-exposed sites. However, an alternative possibility is that mutations in TP53 that stabilize the protein are less common in arsenic-re lated BCCs. Further analysis will be necessary to distinguish between these hypotheses.