Evaluation of superficial basal cell carcinomas after treatment with imiquimod 5% cream or vehicle for apoptosis and lymphocyte phenotyping

Dermatol Surg. 2003 Dec;29(12):1181-6. doi: 10.1111/j.1524-4725.2003.29399.x.

Abstract

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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Aminoquinolines / administration & dosage*
  • Antineoplastic Agents / administration & dosage*
  • Apoptosis*
  • Carcinoma, Basal Cell / drug therapy
  • Carcinoma, Basal Cell / immunology*
  • Carcinoma, Basal Cell / pathology*
  • Dosage Forms
  • Female
  • Humans
  • Imiquimod
  • Lymphocytes*
  • Male
  • Middle Aged
  • Phenotype
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology*

Substances

  • Aminoquinolines
  • Antineoplastic Agents
  • Dosage Forms
  • Imiquimod