Efficacy of imiquimod for the expression of Bcl-2, Ki67, p53 and basal cell carcinoma apoptosis.
BACKGROUND
Imiquimod is a modifier of the immune response that has been proven to be an effective treatment for basal cell carcinoma (BCC). However, its mechanism of action is still unknown.


OBJECTIVE
To determine whether imiquimod modifies the expression of proteins such as Bcl-2, Ki67, p53 and the BCC apoptotic index.


METHODS
Thirty caucasian patients with primary BCCs larger than 8 mm in diameter were included in a double-blind randomized clinical and immunohistochemical study which was designed in a reference university hospital. The 30 BCCs were randomized in two treatment arms between September 2001 and February 2002. Twenty-four BCCs were treated with imiquimod 5% cream and six BCCs with Aldara (3M Pharmaceuticals) excipient. Histological samples were obtained before treatment and on days 8 and 15 during the course of treatment. The BCC expression of Bcl-2, Ki67 and p53 was determined in paraffin samples and the apoptotic index of the BCC was studied using the TUNEL technique (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labelling) in frozen samples. All variables were evaluated quantitatively in fields with a magnification x 400.


RESULTS
The BCCs treated with imiquimod showed a decrease in the expression of Bcl-2 (88.7% before treatment, 61.4% day 15, P = 0.01) and an increase in the apoptotic index (0.53% before treatment, 1.66% day 15, P = 0.002), which were not observed in the BCCs treated with the excipient. Ki67 and p53 did not show significant changes in any group.


CONCLUSIONS
Imiquimod reduces the expression of Bcl-2 in the BCC cells and increases the BCC apoptotic index.
Vidal
D
D
Dermatology Unit, Hospital de la Santa Creu i Sant Pau, C/Sant Antoni Maria Claret 167, Barcelona 08025, Spain. 33053dvs@comb.es
Matías-Guiu
X
X
Alomar
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000634:Aminoquinolines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D000077271:Imiquimod; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism*; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D000077271:Imiquimod