Anagnostopoulos George K, Stefanou Dimitrios, Arkoumani Evdokia, Karagiannis John, Paraskeva Konstantina, Chalkley Lisa, Habilomati Erminia, Tsianos Epaminondas, Agnantis Niki J
Wolfson Digestive Diseases Center, University Hospital, Nottingham, UK.
J Gastroenterol Hepatol. 2008 Apr;23(4):626-31. doi: 10.1111/j.1440-1746.2007.05219.x.
The early indicator for the subject predisposed to gastric cancer is abnormal proliferation of gastric epithelial cells, such as atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia, which have been considered as precancerous lesions of gastric cancer. To determine whether p53 protein, cyclins D1, and D3, and p27(kip1) play a role in the carcinogenesis pathway of gastric cancer, we performed an immunohistochemical study of their expression in gastric precancerous lesions.
A total of 1 45 endoscopic gastric biopsy specimens of AG, IM, and gastric dysplasia were studied. These molecular markers were localized by immunohistochemistry.
P53 was expressed in 15% of cases with gastric dysplasia and not in the pre-dysplastic stages of the gastric mucosa. All cases were concerning high-grade dysplasia. Cyclin D1 protein was almost undetectable in the precancerous lesions of gastric cancer. Cyclin D3 protein overexpression was seen in 10% of biopsies with IM, and 50% of biopsies with gastric dysplasia. High expression of p27(kip1) protein was demonstrated in all cases of chronic gastritis. As atrophy, IM, and dysplasia develop, expression of p27(kip1) protein is suppressed. In total, 15% of dysplastic cases showed no expression of p27(kip1) protein.
(i) P53 mutation must be a late event during the development of gastric cancer. (ii) Cyclin D1 protein overexpression may not play a role in the progression from normal to neoplastic gastric mucosa, while overexpression of cyclin D3 is an earlier event during gastric carcinogenesis, and its role must be further evaluated. (iii) Reduced expression of p27(kip1) is a rather early event in gastric tumorigenesis, before dysplastic changes occur.
易患胃癌个体的早期指标是胃上皮细胞异常增殖，如萎缩性胃炎（AG）、肠化生（IM）和发育异常，这些被视为胃癌的癌前病变。为了确定p53蛋白、细胞周期蛋白D1和D3以及p27（kip1）在胃癌致癌途径中是否起作用，我们对它们在胃癌前病变中的表达进行了免疫组织化学研究。
共研究了145例AG、IM和胃发育异常的内镜胃活检标本。这些分子标志物通过免疫组织化学进行定位。
p53在15%的胃发育异常病例中表达，而在胃黏膜发育异常前期不表达。所有病例均为高级别发育异常。细胞周期蛋白D1蛋白在胃癌前病变中几乎检测不到。细胞周期蛋白D3蛋白在10%的IM活检标本和50%的胃发育异常活检标本中过度表达。p27（kip1）蛋白在所有慢性胃炎病例中均高表达。随着萎缩、IM和发育异常的发展，p27（kip1）蛋白的表达受到抑制。总体而言，15%的发育异常病例未显示p27（kip1）蛋白表达。
（i）p53突变必定是胃癌发生过程中的晚期事件。（ii）细胞周期蛋白D1蛋白过度表达可能在正常胃黏膜向肿瘤性胃黏膜的进展中不起作用，而细胞周期蛋白D3的过度表达是胃癌发生过程中较早的事件，其作用必须进一步评估。（iii）p27（kip1）表达降低是胃癌发生过程中相当早的事件，发生在发育异常改变之前。
