Loss of heterozygosity in actinic keratosis, squamous cell carcinoma and sun-exposed normal-appearing skin in Japanese: difference between Japanese and Caucasians.
Loss of heterozygosity in actinic keratosis, squamous cell carcinoma and sun-exposed normal-appearing skin in Japanese: difference between Japanese and Caucasians.
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DOI：
10.1016/s0304-3835(99)00069-5
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发表时间：
1999-06
期刊：
影响因子：
9.7
通讯作者：
Y. Kushida;H. Miki;M. Ohmori
中科院分区：
文献类型：
--
作者：
Y. Kushida;H. Miki;M. Ohmori
光化性角化病（AK）被认为是鳞状细胞癌（SCC）的先兆。然而，基于流行病学和分子生物学研究，将AK视为癌前病变已变得可疑。我们使用6个微卫星标记分析了37个AK和14个散发性SCC，以阐明任何遗传不稳定性或杂合性丢失（洛）是否与非黑素细胞皮肤肿瘤的发生和进展有关。微卫星不稳定性（MSI）在任何AK或SCC中均未发现，表明遗传不稳定性与散发性非黑素细胞皮肤肿瘤的发生关系不大。37例AK中有7例出现洛，而14例SCC中仅1例出现LOH。洛缺失的发生率明显低于以前报道的白种人，这表明日本人和白种人的AK和SCC的分子发病机制可能不同。本研究中AK的洛缺失频率高于SCC，这支持了以往流行病学和分子生物学研究的结论，即AK不可能发展为SCC。洛缺失也出现在3例组织学正常的皮肤中，表明遗传改变发生在暴露于阳光的皮肤出现组织学变化之前。
Actinic keratosis (AK) has been considered to be a precursor of squamous cell carcinoma (SCC). However, based on epidemiological and molecular studies, it has become questionable to regard AK as a precancerous lesion. We analyzed 37 AKs and 14 sporadic SCCs using six microsatellite markers in order to elucidate if any genetic instability or loss of heterozygosity (LOH) was implicated in tumorigenesis and progression of non-melanocytic skin tumor. Microsatellite instability (MSI) was not found in any of the AKs or SCCs indicating that genetic instability has little implication in the tumorigenesis of sporadic non-melanocytic skin tumor. LOH was found in seven of 37 lesions of AK, but in only one of 14 lesions of SCC. The significantly lower frequency of LOH than that previously reported in Caucasians suggested that the molecular pathogenesis of AKs and SCCs might be different between Japanese and Caucasians. The higher frequency of LOH in AKs than in SCCs in the present study supported the previous epidemiological and molecular studies that AK was not likely to proceed to SCC. LOH was also demonstrated in histologically normal-appearing skin in three cases suggesting that genetic alteration occurs before histological change appears in the sun-exposed skin.