D Vidal1, X Matías-Guiu, A Alomar. 1. Dermatology Unit, Hospital de la Santa Creu i Sant Pau, C/Sant Antoni Maria Claret 167, Barcelona 08025, Spain. 33053dvs@comb.es
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.
RCT Entities:
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: Juliana S de C Monteiro; Susana C P S de Oliveira; João Alves Reis Júnior; Clarissa Araújo Silva Gurgel; Suzana C O Machado de Souza; Antônio Luiz Barbosa Pinheiro; Jean Nunes dos Santos Journal: Lasers Med Sci Date: 2012-09-01 Impact factor: 3.161