Alterations of p53 gene in primary gastric cancer tissues.
Alterations of p53 gene in primary gastric cancer tissues.
复制标题
原发性胃癌组织中p53基因的改变。
作者：
H. Si;Hong Ws;Jang Jj;Lee Ds;Chobanian Ns;Ju Me;Kim Hb;Ha Gw;Park Ic;Chowdhary Ds
本研究采用聚合酶链式反应-单链构象多态性分析(PCR-SSCP)外显子4-8和抗P53抗体DO-7免疫组织化学染色(IHCS)方法，对韩国肿瘤中心医院手术切除的25例胃腺癌组织中P53基因的改变进行研究。应用聚合酶链式反应-单链构象多态性方法检测25例癌组织中有9例(36%)存在p53基因突变，分别位于第4、5、6、7和8外显子。所有组织均行免疫组化染色，11例(44%)染色阳性。在4例患者中，观察到两种方法的结果有差异。1例PCR-SSCP阳性，IHCS阴性，发现外显子7有两个碱基缺失。另3例仅在IHCS中检测到突变，而在PCR-SSCP中未检测到突变。这种差异发生的确切机制目前尚不清楚，尽管这可能是由于本研究中未检测到的其他外显子的突变，或者是因为PCR-SSCP方法的敏感性相对较低。根据病理分期和组织分化程度分析P53基因突变的发生率，但P53基因突变与这些因素之间的差异无统计学意义。联合应用聚合酶链式反应-单链构象多态和免疫组化技术，发现25例原发性胃癌中有48%存在P53基因突变。提示P53基因突变在原发性胃癌中并不少见，P53基因在胃癌的发生发展过程中起着重要作用。
This study was conducted to investigate the p53 gene alterations in 25 surgically-resected gastric adenocarcinomas in the Korea Cancer Center Hospital by polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) for exons 4-8 and immunohistochemical staining (IHCS) with anti-p53 antibody, DO-7. p53 mutations were detected in nine (36%) out of 25 cancer tissues by PCR-SSCP in exon 4-8: 0,1,1,6 and 1 mutations in exons 4,5,6,7 and 8, respectively. All tissues were also tested by IHCS, and positive staining was observed in 11 cases (44%). A discrepancy of the results between the two methods was observed in four cases. In one which showed positivity by PCR-SSCP a negative reaction by IHCS, the two base deletion was observed in exon 7. On the other hand, in three cases the mutation was detected only in IHCS but not in PCR-SSCP. The exact mechanism by which this discrepancy develops is not clear at present, although it may be due to the mutation of other exons not tested in this study or the relatively low sensitivity of the PCR-SSCP method. The incidence of p53 gene mutations was analysed according to pathologic stage and histological differentiation, but no significant difference was observed between the p53 alterations and these factors. By combined use of PCR-SSCP and IHCS, 48% of the 25 primary gastric cancer were considered to have mutations of the p53 gene. These results suggest that p53 mutation is not an infrequent event in primary gastric cancer and the p53 gene plays an important role in the carcinogenesis process of gastric cancer.