Malignant transformation of hyperplastic gastric polyps: An immunohistochemical and pathological study of the changes of neoplastic phenotype
Malignant transformation of hyperplastic gastric polyps: An immunohistochemical and pathological study of the changes of neoplastic phenotype
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DOI：
10.3892/ol.2014.1932
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发表时间：
2014-05-01
期刊：
影响因子：
2.9
通讯作者：
Fujimori, Takahiro
中科院分区：
文献类型：
--
作者：
Imura, Johji;Hayashi, Shinichi;Fujimori, Takahiro
尽管有证据表明胃增生性息肉（HP）恶变是一种罕见的事件，但在诊断过程中必须始终考虑到它。本研究旨在从表型表达、细胞增殖和p53过表达等方面探讨胃增生性息肉恶变的机制。免疫组化的粘蛋白表型标志物，包括MUC 1，MUC 2，MUC 5AC，MUC 6，紧密连接因子（claudin-3，-4和-18），肠表型标志物[尾型同源框2（Cdx 2）]，Ki-67增殖指数和p53过表达，进行了存档标本的胃息肉切除6例。组织学上，这些息肉中存在几种病变的混合成分。此外，癌症成分主要是分化腺癌。免疫组化，所有增生成分表达MUC 5AC，但没有表现出阳性MUC 2。此外，大多数增生成分对claudin-3呈免疫阴性，而在大多数异型增生和癌区域中观察到claudin-3阳性。在大多数病例中也观察到claudin-4的表达，并且在所有病例的增生性、不典型增生和腺癌病变中保留claudin-18。在几乎所有的异型增生和癌样品中检测到Cdx 2的核积累，而在24-80%的异型增生区域和>85%的癌组分中检测到核p53。Ki-67标记指数似乎与肿瘤进展相关。这些观察结果提供了证据表明，胃HP恶性转化的机制可能是通过多步骤癌变发生的，如增生-腺瘤（异型增生）-腺癌序列，并且这些肿瘤细胞在此过程中可能获得各种表型。
In spite of the evidence that the malignant transformation of gastric hyperplastic polyps (HPs) is a rare event, it must always be taken into account during diagnosis. The aim of the current study was to clarify the mechanism of the malignant transformation of gastric hyperplasia polyps, with focus on phenotypic expression, cell proliferation and p53 overexpression. Immunohistochemistry for mucin phenotypic markers, including MUC1, MUC2, MUC5AC, MUC6, tight junction factors (claudin-3, -4 and -18), an intestinal phenotypic marker [caudal type homeobox 2 (Cdx2)], Ki-67 proliferative index and p53 overexpression, was performed on archival specimens of gastric polyps excised from six patients. Histologically, the intermingled components of several lesions were present in these polyps. Furthermore, the cancer components were predominantly differentiated adenocarcinoma. Immunohistochemically, all hyperplastic components expressed MUC5AC, but did not exhibit positivity for MUC2. Additionally, the majority of hyperplastic components were immunonegative for claudin-3, while claudin-3 positivity was observed in the majority of areas of dysplasia and carcinoma. Expression of claudin-4 was also observed in the majority of cases and claudin-18 was preserved in the hyperplastic, dysplastic and adenocarcinomatous lesions of all cases. Nuclear accumulation of Cdx2 was detected in almost all the samples with dysplasia and carcinoma, while nuclear p53 was detected in 24-80% of the dysplastic areas and >85% of the cancer components. The Ki-67 labeling index appeared to correlate with neoplastic progression. The observations provided evidence that the mechanism underlying malignant transformation of gastric HPs may occur by multistep carcinogenesis, such as the hyperplasia-adenoma (dysplasia)-adenocarcinoma sequence, and these neoplastic cells may acquire various phenotypes during this process.