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 di stinct 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 frequent ly lost during the development of SCC are also lost in the VH/VC variant. T wenty-five VH and 17 VC were analyzed for loss of heterozygosity (LOH) at 1 9 loci on 7 chromosome arms using microsatellite analysis. These data were compared with those from 47 reactive hyperplasias, 92 dysplasias (54 low- a nd 38 high-grade), and 41 SCCs. The results showed that VC/VH shared many o f the losses present in dyspiasia/SCC but differed in two aspects. First, V C/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 tha t 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 note d in VH/VC compared with dysplasia/SCC and may indicate human papillomaviru s (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 V H/VC from reactive hyperplasia frequently requires repeated biopsies acid r esults in delay in diagnosis and significantly increased mortality/morbidit y. Microsatellite analysis might facilitate this differential diagnosis.