Altered p53 expression and epidermal cell proliferation is seen in vulval lichen sclerosus

Abstract

Aberrant p53 immunoreactivity has been found in skin premalignancies and dysplasias such as Bowen's disease and actinic keratoses. Vulval lichen sclerosus (LS) has been reported to be pre-malignant, with an association of vulval carcinoma in 3% to 6% of patients. In contrast, non-genital LS appears to have no malignant potential. In this immunocytochemical study, we investigated p53 expression in 10 cases of histologically proven vulval LS and 9 cases of non-genital LS using the murine monoclonal antibody Do-1 raised against recombinant human p53 which reacts with both wild-type and mutant p53. None of the vulval specimens had epithelial dysplasia or malignancy. Normal vulval (7 cases) and non-genital skin (5 cases) were used as tissue controls, respectively. The cell proliferation index was also studied using the MIB 1 monoclonal antibody which detects the cell-cycle associated Ki-67 antigen. The technique of microwave irradiation for antigen unmasking was employed on Formalin-fixed and paraffin-embedded tissues. There was a significant increase in p53 immunoreactivity in vulval LS (32.13 ± 15.11 epidermal cells per 100 basal cells) compared to normal vulval skin (7.52 ± 5.04 epidermal cells per 100 basal cells) (p < 0.001), whereas the MIB 1 labelling index was lower in vulval LS (39.45 ± 15.88 epidermal cells per 100 basal cells) than in normal controls (86.26 ± 32.31 epidermal cells per 100 basal cells) (0.001 < p < 0.01). In contrast, there was no significant difference in p53 immunoreactivity or MIB 1 labelling index between non-genital LS and normal controls. Vulval LS, when compared to non-genital LS (8.76 ± 6.61 epidermal cells per 100 basal cells), also demonstrated a significant increase in P53 immunoreactivity (p < 0.001). The reduced proliferative index in vulval LS may be directly related to its increase in p53 expression and is in keeping with the role ol p53 in the negative regulation of cell proliferation. We propose that the difference in p53 expression may represent a difference in biological behavior between vulval LS and non-genital LS. What role it plays in the evolution of vulval carcinoma in a setting of long standing LS is uncertain.