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Differences in proximal (cardia) versus distal (antral) gastric carcinogenesis via retinoblastoma pathway

机译:通过视网膜母细胞瘤途径的近端(心脏)和远端(肛门)胃癌发生的差异

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AIM: Disruption of cell cycle regulation is a critical event in carcinogenesis, and alteration of the retinoblastoma (pRb) tumour suppressor pathway is frequent. The aim of this study was to compare alterations in this pathway in proximal and distal gastric carcinogenesis in an effort to expiain the observed striking epidemiological differences. METHODS: Immunohistochemistry was performed to investigate expression of p16 and pRb in the following groups of both proximal (cardia) and distal (antral) tissue samples: (a) biopsies showing normal mucosa, (b) biopsies showing intestinal metaplasia and, (c) gastric cancer resection specimens including uninvolved mucosa and tumour. RESULTS: In the antrum there were highly significant trends for increased p16 expression with concomitant (and in the group of carcinomas inversely proportional) decreased pRb expression from normal mucosa to intestinal metaplasia to uninvolved mucosa (from cancer resections) to carcinoma. In the cardia, there were no differences in p16 expression between the various types of tissue samples whereas pRb expression was higher in normal mucosa compared with intestinal metaplasia and tissue from cancer resections. CONCLUSION: Alterations in the pRb pathway appear to play a more significant role in distal gastric carcinogenesis. It may be an early event in the former location since the trend towards p16 overexpression with concomitant pRb underexpression was seen as early as between normal mucosa and intestinal metaplasia. Importantly, the marked differences in expression of pRb and p16 between the cardia and antrum strongly support the hypothesis that tumours of the two locations are genetically different which may account for some of the observed epidemiological differences.
机译:目的:破坏细胞周期调控是致癌作用中的关键事件,视网膜母细胞瘤(pRb)肿瘤抑制途径的改变非常频繁。这项研究的目的是比较近端和远端胃癌发生过程中该途径的变化,以期阐明所观察到的惊人的流行病学差异。方法:采用免疫组织化学方法研究了以下组的近端(心脏)组织和远端(肛门)组织样本中p16和pRb的表达:(a)正常黏膜活检,(b)肠上皮化生活检,(c)胃癌切除标本包括未涉及的粘膜和肿瘤。结果:在胃窦中,p16表达增加的趋势非常明显,与之相反(在癌症组中成反比),pRb表达从正常的粘膜到肠上皮化生到未受累的粘膜(从癌切除术到癌)都呈下降趋势。在the门中,各种类型的组织样品之间的p16表达没有差异,而正常的粘膜中的pRb表达高于肠上皮化生和癌切除组织。结论:pRb途径的改变似乎在远端胃癌发生中起更重要的作用。这可能是前者的早期事件,因为p16过表达与pRb表达不足的趋势被认为早于正常粘膜和肠上皮化生之间。重要的是,the门和胃窦之间pRb和p16表达的显着差异有力地支持了两个位置的肿瘤在遗传上不同的假说,这可能是一些观察到的流行病学差异的原因。

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