[Correlation between aneuploidy of chromosome 17, over-expression of TP53 and TOPIIalpha, and the clinicopathological features and diagnosis of gastric adenocarcinoma].
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).


CONCLUSIONS
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.
Lu
Hai-zhen
HZ
Department of Pathology, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
Wu
Yu-peng
YP
Luo
Wei
W
Han
Ya-ling
YL
Cai
Yan
Y
Xu
Xin
X
Liang
Jing
J
Liu
Shang-mei
SM
Wang
Ming-rong
MR
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D004250:DNA Topoisomerases, Type II