Poh C F, Zhang L, Lam W L, Zhang X, An D, Chau C, Priddy R, Epstein J, Rosin M P
Faculty of Dentistry, University of British Columbia, Vancouver, Canada.
Lab Invest. 2001 Apr;81(4):629-34. doi: 10.1038/labinvest.3780271.
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.
疣状癌（VC）是鳞状细胞癌（SCC）的一种变体，在形态和行为上与SCC不同。VC及其前驱病变疣状增生（VH）发生发展过程中涉及的潜在基因变化尚不清楚。本研究确定了在SCC发生发展过程中经常缺失的染色体区域在VH/VC变体中是否也会缺失。使用微卫星分析对25例VH和17例VC进行分析，检测7个染色体臂上19个位点的杂合性缺失（LOH）。将这些数据与47例反应性增生、92例发育异常（54例低级别和38例高级别）以及41例SCC的数据进行比较：结果显示，VC/VH具有许多发育异常/SCC中存在的缺失，但在两个方面有所不同。首先，与发育异常到SCC中缺失的逐渐积累相比，VC/VH显示出缺失的早期获得。VH的LOH模式与高级别发育异常相似，与反应性增生明显不同。VH中的缺失常涉及多个染色体臂（60%的VH vs 0%的反应性病变）。由于VH中已经存在高度缺失，从VH到VC仅在9p（p = 0.06）和4q（p = 0.05）观察到缺失的轻微升高。其次，与发育异常/SCC相比，VH/VC中17p处的缺失频率显著降低，这可能表明人乳头瘤病毒（HPV）的参与。VH中高危LOH谱的发现可能部分解释了VH所见的高进展风险，也具有潜在的重要临床意义。VH/VC与反应性增生的病理诊断困难，常常需要反复活检，导致诊断延迟，并显著增加死亡率/发病率。微卫星分析可能有助于这种鉴别诊断。
