Allelic loss in human papillomavirus-positive and -negative vulvar squamous cell carcinomas

Vulvar squamous cell carcinoma (VSCC) is a biologically and morphologically diverse disease, consisting of human papillomavirus (HPV)-positive and -ne gative tumors that differ in their morphological phenotypes and associated vulvar mucosal disorders. This study analyzed the frequencies of allelic lo ss (loss of heterozygosity (LOH)) in HPV-positive and -negative VSCCs to id entify potential targets for the study of preinvasive diseases, to determin e whether HPV status influenced patterns of LOH, and to determine whether t hese patterns differed from HPV-positive tumors of another genital site, ce rvical squamous cell carcinomas (CSCC), DNA extracted from microdissected a rchival sections of two index tumors, one each HPV negative and positive, w as analyzed for LOH at 65 chromosomal loci. Loci scoring positive with eith er sample were included in an analysis of 14 additional cases that were als o typed for HPV. Frequencies of LOH at loci were computed in a panel of HPV -positive and -negative VSCCs. Twenty-nine loci demonstrated LOH on the ini tial screen and were used to screen the remaining 14 tumors. High frequenci es of LOH were identified, some of which were similar to a prior karyotypic study (3P, 5q, 8p, 10q, 15q, 18q, and 22q) and others of which had not pre viously been described in VSCC (1q, 2q, 8q, 10p, 11p, 11q, 17p, and 21q). W ith the exception of 5q and 10p, there were no significant associations bet ween frequency of LOH and HPV status in VSCC, LOH at 3p and 11q were freque nt in both VSCC and CSCC; however, allelic losses at several sites, includi ng 5q, 8q, 17p, 21q, and 22q, were much more common in VSCC. VSCCs exhibit a broad range of allelic losses irrespective of HPV status, with high frequ encies of LOH on certain chromosomal arms. This suggests that despite their differences in pathogenesis, both HPV-positive and -negative VSCCs share s imilarities in type and range of genetic losses during their evolution. Whe ther the different frequencies of LOH observed between VSCC and CSCC are re al or reflect differences in stage and/or tumor size remains to be determin ed by further comparisons, The role of these altered genetic loci in the ge nesis of preinvasive vulvar mucosal lesions merits additional study.