[17号染色体非整倍体、TP53和TOPIIα过表达与胃腺癌临床病理特征及诊断的相关性]

Lu Hai-zhen, Wu Yu-peng, Luo Wei, Han Ya-ling, Cai Yan, Xu Xin, Liang Jing, Liu Shang-mei, Wang Ming-rong

Department of Pathology, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.

Zhonghua Zhong Liu Za Zhi. 2009 Oct;31(10):754-8.

OBJECTIVE

The purpose of this study was to investigate the markers which can be used in auxiliary diagnosis of gastric adenocarcinoma (GAC), and their correlation with their clinicopathological features.

METHODS

122 surgical specimens including 99 gastric adenocarcinoma (GAC), 18 adjacent mucosa and 5 distal normal mucosa were collected, and analyzed by in situ hybridization (FISH). The centromere probe cen17, specific for chromosome 17, which was reported to be frequently amplified in GAC, was selected for the FISH analysis. The clinicopathological features of the 99 GAC cases were reviewed, and the level of TP53 and TOPIIalpha gene expression, located in chromosome 17, was detected using tissue micro-array (TMA), compared with that of corresponding adjacent normal mucosa. Data were analyzed with SPSS 11.5 for Windows.

RESULTS

The statistical results of FISH and TMA showed that 58.6% of cen17 in tumor tissues were aneuploid, and 45.5% of TP53 and 84.7% of TOPIIalpha were over-expressed in GAC samples, significantly higher than those in non-tumor gastric mucosa (0, 12.1% and 14.1%, respectively) (P = 0.000). 58 GAC tissues were aneuploid of cen17, including 26 cases TP53-positive and 49 cases TOPIIalpha-positive. The expression of TP53 in non-tumor gastric mucosa with dysplasia was significantly higher than that in the mucosa without dysplasia (P = 0.009). Aneuploidy of cen17 was more frequent in grade 1 or 2 than in grade 3 GAC (P < 0.05). Higher frequency of aneuploidy of cen17 was also observed in the gastric cardia than in pylorus (P < 0.05), while no correlation was found between aneuploidy of cen17 and age, sex of patients, lymph node metastasis, and clinical stage of tumors. Over-expression of TP53 protein was associated with the size of tumors (P < 0.05). In addition, a negative correlation was observed between over-expression of TOPIIalpha and lymph node metastasis (LNM) as well as TNM classification (P < 0.05).

CONCLUSION

Detection of aneuploidy of cen17 as well as over-expression of TP53 and TOPIIalpha may be helpful in the diagnosis and prognostic prediction of gastric adenocarcinoma.

目的

本研究旨在探讨可用于胃腺癌（GAC）辅助诊断的标志物及其与临床病理特征的相关性。

方法

收集122份手术标本，包括99例胃腺癌（GAC）、18例癌旁黏膜和5例远端正常黏膜，采用原位杂交（FISH）进行分析。选择对17号染色体特异的着丝粒探针cen17用于FISH分析，该探针据报道在GAC中常发生扩增。回顾99例GAC病例的临床病理特征，使用组织芯片（TMA）检测位于17号染色体上的TP53和TOPIIalpha基因表达水平，并与相应的癌旁正常黏膜进行比较。数据采用SPSS 11.5 for Windows软件进行分析。

结果

FISH和TMA的统计结果显示，肿瘤组织中58.6%的cen17为非整倍体，GAC样本中45.5%的TP53和84.7%的TOPIIalpha过度表达，显著高于非肿瘤胃黏膜（分别为0、12.1%和14.1%）（P = 0.000）。58例GAC组织为cen17非整倍体，其中26例TP53阳性，49例TOPIIalpha阳性。发育异常的非肿瘤胃黏膜中TP53的表达显著高于无发育异常的黏膜（P = 0.009）。cen17非整倍体在GAC 1级或2级中比3级更常见（P < 0.05）。贲门部cen17非整倍体的频率也高于幽门部（P < 0.05），而cen17非整倍体与患者年龄、性别、淋巴结转移及肿瘤临床分期之间未发现相关性。TP53蛋白的过度表达与肿瘤大小相关（P < 0.05）。此外，TOPIIalpha的过度表达与淋巴结转移（LNM）及TNM分类呈负相关（P < 0.05）。