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 genesis of sporadic, presumably mainly sunlight-related, basal cell carcinoma (BCC). However, its role in arsenic-related BCCs is not clear, although the trivalent form of arsenic has been long recognized as a cause of BCC. Arsenic treatment has been shown to cause hypermethylation of the TP53 gene in 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 pattern is consistent with gene silencing.


METHODS
A research institute and hospital in Australia.


METHODS
One hundred seventeen white patients with 121 sporadic BCCs and 21 white patients with 92 arsenic-related BCCs.


METHODS
The expression and the intensity of p53 were scored semiquantitatively. Statistical analysis was performed using the chi2 test.


RESULTS
Arsenic-related BCCs express p53 less often and at a lower intensity than sporadic BCCs (P = .001; 2-tailed test). The BCCs from sun-exposed sites, whether arsenic related or sporadic, more frequently showed overexpression 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 p53 than the less aggressive forms (P = .04; 2-tailed chi2 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-related BCCs. Further analysis will be necessary to distinguish between these hypotheses.
Boonchai
W
W
The Queensland Institute of Medical Research, University of Queensland, Brisbane, Australia.
Walsh
M
M
Cummings
M
M
Chenevix-Trench
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001151:Arsenic / Q000009:adverse effects*; D002273:Carcinogens / Q000009:adverse effects*; D002280:Basal Cell Carcinoma / Q000139:chemically induced / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
D002273:Carcinogens; D016159:Tumor Suppressor Protein p53; D001151:Arsenic