Monoclonal origin of vulvar intraepithelial neoplasia and some vulvar hyperplasias.
Squamous neoplasms of the female genital tract, including vulvar intraepithelial neoplasia, presumably are derived from a single cell. This study addressed this hypothesis and determined the clonal status of other squamous epithelial alterations associated with vulvar carcinoma, including hyperplasia and lichen sclerosis. X chromosome inactivation patterns of 22 epithelial lesions and matched normal epithelium were determined using a polymerase chain reaction (PCR)-based assay targeting 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 lesional and control were unskewed, and 3) unknown, if both lesion and control tissues were skewed toward the same allele. Two cases were excluded because of noninformative homozygous HUMARA alleles. Of 8 vulvar intraepithelial neoplasias analyzed, 7 were scored monoclonal and 1 polyclonal. Of 12 hyperplasias, 6 were monoclonal, including one with lichen sclerosis, 2 were polyclonal, and in 4, the clonal status could not be determined. The PCR-based clonal assay supports a monoclonal derivation for vulvar intraepithelial neoplasia and, in some cases, vulvar hyperplasia, and lichen sclerosis. The finding of monoclonal hyperplasia and lichen sclerosis suggests that clonal expansion may evolve before the development of morphological atypia in these epithelia.
Tate
J E
JE
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Mutter
G L
GL
Boynton
K A
KA
Crum
C P
CP
D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology*; D002999:Clone Cells / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D014844:Vulva / Q000473:pathology*; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000473:pathology*; D014960:X Chromosome / Q000473:pathology