Clonal nature of seborrheic keratosis demonstrated by using the polymorphism of the human androgen receptor locus as a marker

We evaluated the clonality of seborrheic keratoses using a polymorphism due to the random inactivation of one of two X chromosomes in females. Thirty- eight seborrheic keratoses obtained from the skin of females with polymorph ism of the human androgen receptor (HUMARA) locus were examined by a fluore scent polymerase chain reaction procedure, which allowed accurate measureme nt of the peak intensities of each HUMARA allele, The epithelial portion of seborrheic keratosis and normal control epidermis adjacent to the seborrhe ic keratosis were removed by laser capture microdissection. As biopsied spe cimens of seborrheic keratoses contained small amounts of normal epidermis, the effect of digestion by a restriction enzyme (HhaI) recognizing the non methylated active sites was compared between seborrheic keratoses and norma l control epidermis in only five seborrheic keratosis cases. Disappearance or significant reduction in intensity of one of two HUMARA alleles was obse rved after HhaI digestion in seborrheic keratoses, but not in the normal co ntrol epidermis. Although the skewing of the polymorphism was not corrected by the normal control epidermis in the remaining 33 seborrheic keratosis c ases, one of two HUMARA peaks practically disappeared after HhaI digestion in 20 of 33 seborrheic keratosis cases. In total, 25 of 38 seborrheic kerat oses were considered to be monoclonal. The histologic type of seborrheic ke ratoses did not affect clonality.