A high frequency of allelic loss in oral verrucous lesions may explain malignant risk

Verrucous carcinoma (VC), a variant of squamous cell carcinoma (SCC), is distinct from SCC in morphology and behavior. The underlying genetic changes involved in the development of VC and its precursor verrucous hyperplasia (VH) are unknown. This study determined whether chromosomal regions frequently lost during the development of SCC are also lost in the VH/VC variant. Twenty-five VH and 17 VC were analyzed for loss of heterozygosity (LOH) at 19 loci on 7 chromosome arms using microsatellite analysis. These data were compared with those from 47 reactive hyperplasias, 92 dysplasias (54 low- and 38 high-grade), and 41 SCCS: The results showed that VC/VH shared many of the losses present in dysplasia/SCC but differed in two aspects. First, VC/VH showed early acquisition of loss, compared with a gradual accumulation of losses from dysplasias to SCC. The LOH pattern of VH was similar to that of high-grade dysplasia and sharply different from reactive hyperplasia. The loss in VH often involved multiple arms (in 60% of VH vs 0% of reactive lesions). Only a marginal elevation of loss was observed at 9p (p = 0.06) and 4q (p = 0.05) from VH to VC because of the high degree of loss already present in VH. Second, a strikingly lower frequency of loss at 17p was noted in VH/VC compared with dysplasia/SCC and may indicate human papillomavirus (HPV) involvement. The finding of high-risk LOH profiles in VH may partly account for the high-progression risk seen for VH and also has potentially important clinical implications. The difficult pathological diagnosis of VH/VC from reactive hyperplasia frequently requires repeated biopsies and results in delay in diagnosis and significantly increased mortality/morbidity. Microsatellite analysis might facilitate this differential diagnosis.