Evaluation of superficial basal cell carcinomas after treatment with imiquimod 5% cream or vehicle for apoptosis and lymphocyte phenotyping.
OBJECTIVE
To characterize the immune response and the apoptotic pathways that result in regression of imiquimod-treated basal cell carcinomas (BCCs).


METHODS
The trial was conducted as an open-label, matched controlled, nonrandomized study. Twelve patients were assigned as either active-treatment patients or matched control subjects. After treatment, lesions were excised and stained for CD20, CD3, CD4, CD56, bcl-2, bax, caspase-3, and p53. Additionally, a DNA fragmentation assay was performed using the terminal deoxynucleotidyltransferase-mediated dUTP nick-end-labeling method.


RESULTS
All vehicle-treated BCCs (six of six) had residual tumor compared with four of six imiquimod-treated BCCs. A dense mononuclear infiltrate surrounded all of the imiquimod-treated tumors and only one of six vehicle-treated BCCs. Staining for CD20, CD3, and CD4 revealed that the infiltrate consisted primarily of T-helper lymphocytes; however, a significant portion of the cells stained positively for CD56, indicating the presence of natural killer cells. Imiquimod-treated BCCs stained more strongly for caspase-3 and to a lesser degree p53 as compared with vehicle-treated BCCs. No differences were seen in either bax or bcl-2 staining. Minimal apoptosis was seen with the terminal deoxynucleotidyltransferase-mediated dUTP nick-end-labeling assay in either group.


CONCLUSIONS
This study provides evidence that imiquimod's antitumorigenic effects are mediated via up regulation of local interferon-alpha levels and supports previous work, suggesting that increased natural killer cell activity may be an important factors explaining both spontaneous regression and IFN-alpha induced regression of BCC.
Sullivan
Tory P
TP
Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, PO Box 016250 (R-250), Miami, FL 33101, USA. tsullivan@med.miami.edu
Dearaujo
Tami
T
Vincek
Vladimir
V
Berman
Brian
B
D000368:Aged; D000634:Aminoquinolines / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis; D002280:Basal Cell Carcinoma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D004304:Dosage Forms; D005260:Female; D006801:Humans; D000077271:Imiquimod; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D004304:Dosage Forms; D000077271:Imiquimod