胃癌17号染色体异倍体改变及TP53和拓扑异构酶Ⅱα蛋白过表达与病理诊断的相关性

Correlation between aneuploidy of chromosome 17, over-expression of TP53 and TOP H a, and the clinicopathological features and diagnosis of gastric adenocarcinoma

目的探讨胃腺癌17号染色体倍性改变及TP53和拓扑异构酶Ⅱα（TOPⅡα）蛋白的表达在胃癌病理诊断中的意义。方法选取胃癌中异倍体出现频率较高的17号染色体着丝粒探针，应用荧光原位杂交技术对99例胃腺癌、18例癌旁组织及5例远端胃黏膜进行分析。复阅相应肿瘤患者癌和癌旁组织病理切片，构建组织微阵列，对位于17号染色体上的TP53和TOPⅡα蛋白进行免疫组织化学检测和分析。应用SPSS11．5软件进行统计。结果胃癌和癌旁组织的17号染色体异倍体发生频率及TP53和TOPⅡα蛋白表达率分别为58．6％、45．5％、84．7％和0、12．1％、14．1％，差异有统计学意义（P=0．000）。在58例检测到17号染色体异倍体的胃癌组织中，TP53表达阳性26例，TOPⅡα表达阳性49例。TP53在伴有不典型增生的癌旁黏膜中的表达率高于无不典型增生的癌旁黏膜（P=0．009）。高、中分化腺癌的17号染色体异倍体发生率（69．8％）显著高于低分化腺癌（50．0％，P=0．048）。贲门部胃腺癌的17号染色体异倍体发生率高于幽门部（P〈0．05）。肿瘤≥5cm患者的TP53表达高于肿瘤〈5cm者（P=0．034）。TOPⅡα蛋白在淋巴结转移数目≤6枚患者和pTNM分期早的患者中表达较高（P=0．010，P=0．003）。17号染色体异倍体及TP53和TOPⅡα蛋白表达之间无相关性。结论17号染色体异倍体及TP53、TOPⅡα蛋白表达的检测对胃腺癌辅助诊断及预后判断具有一定意义。

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 cenl7, 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 TOP Ⅱα gene expression, located in chromosome 17, was detected using tissue microarray （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 TOP Ⅱα 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 TOP Ⅱα- 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 TOP Ⅱα 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 TOP Ⅱα may be helpful in the diagnosis and prognostic prediction of gastric adenocarcinoma.