Reconstruction of the two-dimensional distribution of p53 positive staining patches in sun-exposed morphologically normal skin

1,320 serial sections were microscopically examined from 11 excisions of human skin with a variety of neoplastic lesions. In total about 1 cm(2) of morphologically normal epidermis was scrutinized. The emphasis was on the topography of epidermal 'p53 patches' of morphologically normal keratinocytes apparently driven into clonal expansion by a mutation of the p53 gene or an analogous mechanism causing constitutive nuclear accumulation of p53. The p53 patches were only rarely in contact with dysplasia or carcinoma in situ supporting previous somatic genetic evidence that patches are not common precursors of squamous cell neoplasia. The size of the p53 patches varied from 0.03 to at least 12 mm(2). About 34% of epidermis was covered by p53 patches deduced to be originally derived from an average of 40 cells per cm(2) by clonal expansion. This implies that a large number of skin cells are at risk of contracting further mutations in the p53 gene and other parts of the genome, if the 'guardian of the genome hypothesis' of the p53 gene is correct and exposure to sun-light continues. This finding together with calculations based on number of basal cells/mm(2) skin area suggest that prevalence of mutations which apparently drive stem cells into clonal growth is about 1:15,000 stem cells in 70-80 years old Caucasian sun-exposed skin at latitude 60 degrees North.