Wu M S, Shun C T, Sheu J C, Wang H P, Wang J T, Lee W J, Chen C J, Wang T H, Lin J T
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei.
J Gastroenterol Hepatol. 1998 Mar;13(3):305-10. doi: 10.1111/j.1440-1746.1998.01560.x.
Although the mechanism remains obscure, two histological subtypes of gastric carcinoma (GC), the diffuse and intestinal types, differ drastically in epidemiological, clinical, pathological and biological characteristics. We investigated whether the genetic alterations of several oncogenes and tumour suppressor genes could be correlated with the two histological subtypes. In 60 patients with GC, the overexpression of mutant p53 and c-erbB-2 oncoproteins was studied using immunohistochemical stains. Mutations of the p15 and p16 tumour suppressor genes were assessed by polymerase chain reaction, Southern blotting, and direct DNA sequencing. Overexpression of c-erbB-2 and p53 was found in 21 (35.0%) and 27 (45.0%) patients, respectively. Overexpression of the c-erbB-2 oncoprotein was more common in the intestinal type (15/32, 46.9%) and the advanced stage (19/45, 42.2%) than in the diffuse type (6/28, 21.4%) and the early stage (2/15, 13.3%) of GC (P<0.05). Similarly, p53 overexpression was more frequently found in the intestinal type (19/32, 59.4%) and the advanced stage (24/45, 53.3%) than in the diffuse type (8/28, 28.6%) and the early stage (3/15, 20.0%) of GC (P<0.05). Homozygous deletions of p16 in exon 1 were found in six (10.0%) patients. Five of them had the intestinal-type advanced GC. Neither point mutations of p16 nor alterations of p15 were detected. The frequency of alterations of p53, c-erbB-2, and p16 was not related to sex and Helicobacter pylori infection. No correlation of genetic changes between any two genes was observed. Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC. Moreover, overexpression of c-erbB-2 and p53 is frequently encountered in the intestinal-type advanced GC. Alterations of p53, c-erbB-2 and p16 genes may function independently of each other in gastric carcinogenesis. The association between genetic alterations and histological subtypes supports the notion that a distinct pathogenesis may exist in different histological subtypes.
尽管其机制仍不清楚，但胃癌（GC）的两种组织学亚型，即弥漫型和肠型，在流行病学、临床、病理和生物学特征上有很大差异。我们研究了几种癌基因和肿瘤抑制基因的基因改变是否与这两种组织学亚型相关。在60例GC患者中，使用免疫组织化学染色研究了突变型p53和c-erbB-2癌蛋白的过表达情况。通过聚合酶链反应、Southern印迹和直接DNA测序评估p15和p16肿瘤抑制基因的突变情况。分别在21例（35.0%）和27例（45.0%）患者中发现c-erbB-2和p53过表达。c-erbB-2癌蛋白的过表达在GC的肠型（15/32，46.9%）和晚期（19/45，42.2%）比弥漫型（6/28，21.4%）和早期（2/15，13.3%）更常见（P<0.05）。同样，p53过表达在GC的肠型（19/32，59.4%）和晚期（24/45，53.3%）比弥漫型（8/28，28.6%）和早期（3/15，20.0%）更常见（P<0.05）。在6例（10.0%）患者中发现p16外显子1的纯合缺失。其中5例患有肠型晚期GC。未检测到p16的点突变和p15的改变。p53、c-erbB-2和p16的改变频率与性别和幽门螺杆菌感染无关。未观察到任何两个基因之间的基因变化相关性。我们的初步结果表明，p15基因的改变在胃癌发生中并不重要，而p16基因罕见的纯合缺失在肠型GC的肿瘤进展中起有限作用。此外，c-erbB-2和p53过表达在肠型晚期GC中经常出现。p53、c-erbB-2和p16基因的改变在胃癌发生过程中可能彼此独立发挥作用。基因改变与组织学亚型之间的关联支持了不同组织学亚型可能存在不同发病机制的观点。
