Efficacy of imiquimod for the expression of Bcl-2, Ki67, p53 and basal cell carcinoma apoptosis.

Abstract

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.

OBJECTIVES:

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

PATIENTS AND 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.

• Authors: D Vidal, X Matías-Guiu, A Alomar
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 151 Issue 3 Pg. 656-62 (Sep 2004) ISSN: 0007-0963 [Print] England
• PMID: 15377354 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Aminoquinolines
• Antineoplastic Agents
• Ki-67 Antigen
• Neoplasm Proteins
• Proto-Oncogene Proteins c-bcl-2
• Tumor Suppressor Protein p53
• Imiquimod

Topics

• Adult
• Aged
• Aged, 80 and over
• Aminoquinolines (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Basal Cell (metabolism, pathology)
• Cell Division (drug effects)
• Double-Blind Method
• Down-Regulation (drug effects)
• Female
• Humans
• Imiquimod
• Immunoenzyme Techniques
• Ki-67 Antigen (drug effects, metabolism)
• Male
• Middle Aged
• Neoplasm Proteins (drug effects, metabolism)
• Prospective Studies
• Proto-Oncogene Proteins c-bcl-2 (drug effects, metabolism)
• Skin Neoplasms (metabolism, pathology)
• Tumor Suppressor Protein p53 (drug effects, metabolism)