Craanen M E, Blok P, Dekker W, Offerhaus G J, Tytgat G N
Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.
Gut. 1995 Jun;36(6):848-52. doi: 10.1136/gut.36.6.848.
p53 Protein accumulation in early gastric carcinoma was studied in relation to the histological type (Lauren classification) and the type of growth pattern, including the chronology of p53 protein accumulation during carcinogenesis. Forty five, paraffin embedded gastrectomy specimens from early carcinomas were examined for the presence of chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. The Lauren type and the type of growth pattern were reassessed for all early carcinomas. p53 Protein accumulation was examined using the monoclonal antibody DO-7. Complete absence of p53 protein accumulation was observed in normal gastric mucosa, chronic atrophic gastritis, and intestinal metaplasia, irrespective of subtype. In gastric dysplasia (one mild, two moderate, and one severe), only severe dysplasia was p53 positive. Intestinal type (n = 20) and diffuse type early gastric carcinomas (n = 25) were p53 positive in 70% and 52% of cases, respectively. Both tumour types differed significantly in the percentage of p53 positive tumour cells per tumour (p < 0.01) and in staining intensity (p < 0.05). No significant difference in p53 protein accumulation was found between early carcinomas with different types of growth pattern. It is concluded that p53 protein accumulation--usually reflecting missense p53 gene mutation--seems to be a late event in gastric carcinogenesis. Moreover, it is suggested that missense p53 gene mutation occurs in a final pathway common to both intestinal and diffuse type of early gastric carcinoma. Finally, the types of growth pattern do not seem to differ in p53 protein accumulation.
研究了早期胃癌中p53蛋白积累与组织学类型(劳伦分类法)及生长模式类型的关系,包括癌变过程中p53蛋白积累的时间顺序。对45例早期癌石蜡包埋胃切除标本检查了慢性萎缩性胃炎、肠化生亚型及发育异常的存在情况。对所有早期癌重新评估了劳伦类型及生长模式类型。使用单克隆抗体DO-7检测p53蛋白积累情况。在正常胃黏膜、慢性萎缩性胃炎及肠化生中,无论亚型如何,均未观察到p53蛋白积累完全缺失。在胃发育异常(1例轻度、2例中度和1例重度)中,仅重度发育异常p53呈阳性。肠型早期胃癌(n = 20)和弥漫型早期胃癌(n = 25)中,p53阳性病例分别为70%和52%。两种肿瘤类型在每个肿瘤中p53阳性肿瘤细胞百分比(p < 0.01)及染色强度(p < 0.05)方面均有显著差异。不同生长模式类型的早期癌在p53蛋白积累方面未发现显著差异。结论是,p53蛋白积累——通常反映错义p53基因突变——似乎是胃癌发生过程中的晚期事件。此外,提示错义p53基因突变发生在肠型和弥漫型早期胃癌共同的最终途径中。最后,生长模式类型在p53蛋白积累方面似乎没有差异。