MONOCLONAL ORIGIN OF VULVAR INTRAEPITHELIAL NEOPLASIA AND SOME VULVARHYPERPLASIAS

Squamous neoplasms of the female genital tract, including vulvar intra epithelial neoplasia. Presumably are derived front a single cell. This study addressed this hypothesis and determined the clonal status of o ther squamous epithelial alterations associated with vulvar carcinoma, including hyperplasia and lichens sclerosis. X chromosome inactivatio n patterns of 22 epithelial lesions and matched normal epithelium were determined using a polymerase chain reaction (PCR)-based assay target ing the X-linked human androgen receptor gene (HUMARA). Clonality was inferred by comparing matched lesional and control tissues as follows: 1) monoclonal, if intensity of either PCR product was skewed relative to normal reference epithelium (control), 2) polyclonal, if both lesi onal and control were unskewed, and 3) unknown, if both lesion and con trol tissues were skewed toward the same allele. Two cases were exclud ed because of noninformative homozygous HUMARA alleles. Of 8 vulvar in tra-epithelial neoplasias analyzed, 7 were scored monoclonal and 1 pol yclonal. Of 12 hyperplasias, 6 were monoclonal, including one with lic hen sclerosis, 2 were polyclonal, and in 4, the clonal status could no t be determined. The PCR-based clonal assay supports a monoclonal deri vation for vulvar intraepithelial neoplasia and in some cases, vulvar hyperplasia, and lichen sclerosis. The finding of monoclonal hyperplas ia and lichen sclerosis suggests that clonal expansion may evolve befo re the development of morphological atypia in these epithelia.