Genetic steps in the development of squamous cell carcinoma of the esophagus
Genetic steps in the development of squamous cell carcinoma of the esophagus
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DOI：
10.1016/s1383-5742(00)00019-3
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发表时间：
2000-04-01
影响因子：
5.3
通讯作者：
Hollstein, M
中科院分区：
文献类型：
--
作者：
Mandard, AM;Hainaut, P;Hollstein, M
食管鳞状细胞癌（ESCC）是一种常见的癌症形式，在地理分布上显示出惊人的变化，反映了暴露于特定的环境因素，仍然定义不清。ESCC的发展是一系列组织病理学变化的结果，通常涉及食管炎、萎缩、轻度至重度异型增生、原位癌以及最后的浸润性癌症。与ESCC发展相关的遗传变化包括p53基因突变、通过几种机制（p16 MTS 1失活、细胞周期蛋白D1扩增、RE改变）破坏G1期细胞周期控制、癌基因激活（例如，EGFR，c-MYC）和几种肿瘤抑制基因的失活。染色体17 q25上的杂合性缺失与侵填体病有关，侵填体病是一种罕见的常染色体显性综合征，与ESCC的高易感性有关。该基因座是否也参与散发性ESCC仍有待阐明。慢性食管炎是食管鳞癌高危人群中的常见病。这些病变通常显示p53蛋白的局灶性积聚，并且在某些情况下。在肿瘤边缘的食管炎区发现了斑片状的阳性细胞含有p53基因的突变。这一观察结果与食管的实地癌变一致，并表明食管炎可能是早期发现ESCC以及干预策略的一个有趣的目标。(C)2000 Elsevier Science B. V.保留所有权利。
Esophageal squamous cell carcinoma (ESCC) is a frequent form of cancer that shows striking variations in geographic distribution, reflecting exposure to specific environmental factors that are still poorly defined. ESCC develops as the result of a sequence of histopathological changes that typically involves esophagitis, atrophy, mild to severe dysplasia, carcinoma in situ and finally, invasive cancer. Genetic changes associated with the development of ESCC include mutation of the p53 gene, disruption of cell-cycle control in G1 by several mechanisms (inactivation of p16MTS1, amplification of Cyclin D1, alterations of RE), activation of oncogenes (e.g., EGFR, c-MYC) and inactivation of several tumor suppressor genes. Loss of heterozygosity on chromosome 17q25 has been linked with tylosis, a rare autosomal dominant syndrome associated with high predisposition to ESCC. Whether this locus is also involved in sporadic ESCC remains to be elucidated. Chronic esophagitis is a frequent occurrence in populations at high risk of ESCC. These lesions often show focal accumulation of p53 protein and in some instances. patches of positive cells in esophagitis area at the margins of tumors were found to contain a mutation in the p53 gene. This observation is consistent with field cancerization in the esophagus and suggests that esophagitis may represent an interesting target for early detection of ESCC as well as for intervention strategies. (C) 2000 Elsevier Science B.V. All rights reserved.