This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (26)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Dermatology, Other  • Alert me on articles by topic

Waranya Boonchai, MD; Michael Walsh, BSC; Margaret Cummings, FRCPath, PhD; Georgia Chenevix-Trench, PhD

Arch Dermatol. 2000;136:195-198.

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.

Setting  A research institute and hospital in Australia.

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

Main Outcome Measures  The expression and the intensity of p53 were scored semiquantitatively. Statistical analysis was performed using the ² 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 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-related BCCs. Further analysis will be necessary to distinguish between these hypotheses.

From The Queensland Institute of Medical Research (Drs Boonchai and Chenevix-Trench) and the Department of Pathology, University of Queensland (Mr Walsh and Drs Cummings and Chenevix-Trench), Brisbane, Queensland, Australia.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

P53 alterations in bladder tumors from arsenic and tobacco exposed patients
Moore et al.
Carcinogenesis 2003;24:1785-1791.
ABSTRACT | FULL TEXT  

Invited Reviews: Carcinogenic and Systemic Health Effects Associated with Arsenic Exposure--A Critical Review
Tchounwou et al.
Toxicol Pathol 2003;31:575-588.
ABSTRACT  

Carcinogenicity of dimethylarsinic acid in p53 heterozygous knockout and wild-type C57BL/6J mice
Salim et al.
Carcinogenesis 2003;24:335-342.
ABSTRACT | FULL TEXT  

Coordination of Altered DNA Repair and Damage Pathways in Arsenite-Exposed Keratinocytes
Hamadeh et al.
Toxicol Sci 2002;69:306-316.
ABSTRACT | FULL TEXT