Differentiation reprogramming in gastric intestinal metaplasia and dysplasia: role of SOX2 and CDX2
Differentiation reprogramming in gastric intestinal metaplasia and dysplasia: role of SOX2 and CDX2
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DOI：
10.1111/his.12544
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发表时间：
2015-02-01
期刊：
影响因子：
6.4
通讯作者：
Almeida, Raquel
中科院分区：
文献类型：
--
作者：
Camilo, Vania;Garrido, Monica;Almeida, Raquel
目的：由CDX 2从头表达引起的肠化生（IM）和异型增生是胃癌的前体病变，与癌症发展风险增加相关。有许多证据表明转录因子SOX 2在胃分化中的作用。本研究的目的是试图建立SOX 2与CDX 2的关系，以及与胃癌发生的分化重编程的关系，以评估它们在IM和异型增生中的参与。方法和结果：胃的特征应用免疫组化方法检测正常胃粘膜、55例IM病灶和26例异型增生病灶中的SOX 2、MUC5AC和MUC6及肠道标志物CDX2和MUC2。SOX 2在正常胃粘膜中表达，在假定的干细胞隔室中，并且在7%的完全（MUC5AC阴性）和85%的不完全（MUC5AC阳性）IM亚型中维持。12%的异型增生病变表达SOX 2，与MUC5AC的相关性消失。CDX2存在于所有的IM和异型增生lesions.Conclusions：SOX 2与胃分化不完全IM和不典型增生的进展中丢失，而CDX2获得从头IM和维持在异型增生。这表明胃和肠分化程序之间的平衡影响胃癌级联进展。
Aims: Intestinal metaplasia (IM), which results from de-novo expression of CDX2, and dysplasia are precursor lesions of gastric cancer that are associated with an increased risk for cancer development. There is much evidence suggesting a role for the transcription factor SOX2 in gastric differentiation. The aim of this study was to attempt to establish the relationship of SOX2 with CDX2 and with the differentiation reprogramming that characterizes gastric carcinogenesis, to assess their involvement in IM and dysplasia.Methods and results: Characterization of gastric (SOX2, MUC5AC, and MUC6) and intestinal (CDX2 and MUC2) markers in normal gastric mucosa, in 55 foci of IM and in 26 foci of dysplasia, was performed by immunohistochemistry. SOX2 was expressed in the normal gastric mucosa, in the presumptive stem cell compartment, and was maintained in 7% of the complete (MUC5AC-negative) and 85% of the incomplete (MUC5AC-positive) IM subtypes. Twelve per cent of the dysplastic lesions expressed SOX2, and the association with MUC5AC was lost. CDX2 was present in all IMs and dysplastic lesions.Conclusions: SOX2 is associated with gastric differentiation in incomplete IM and is lost in the progression to dysplasia, whereas CDX2 is acquired de novo in IM and maintained in dysplasia. This suggests that the balance between gastric and intestinal differentiation programmes impacts on the gastric carcinogenesis cascade progression.