| Objective:Extragastrointestinal stromal tumor are a group of mesenchymal tumor which are originated from the abdominal cavity or retroperitoneal soft tissue and unrelated to the abdominal wall and serosal surface of digestive tract.The purpose of this study is to investigate the status of p16 gene deletion and chromosome 17 aneuploidy change in EGIST and the relationship with p16 and p53 protein expression, and to analyse the correlation between the three types of multi-drug resistance gene product(P-gp,GST-πand TopoⅡ),to provide valuable reference information for related drug treatment of EGIST after operation.Objects and Methods:30 cases of EGIST samples were collected from 2004-2008, all EGIST to confirm by histology and immunohistochemistry and then applying fluorescence in situ hybridization(FISH) technique to detect hybridism status of p 16/CSP 17 two-color hybridization probe with the tumor cells on paraffin sections,and detecting the expression of p16,p53 protein as well as the three multidrug resistance gene produce(P-gP,GST-πand TopoⅡ) of 30 cases of EGIST by immunohistoc -hemistry method,Statistical analysis was performed using the SPSS 11.5 software.Results:(1)The results of FISH showed that p16 gene deletion was identified in 18 cases(60.0%,18/30).Immunohistohemocal study showed that 22 cases(73.3%,22/30) with low or absent p16 expression,the Common missing cases was 16.p16 gene deletion was no significant difference with clinicopathological parameters including age, sex,tumor location,cell type,tumor size,number of mitotic figures and necros neither or not(P＞0.05),but p16 protein expression was significantly correlated with pathological mitotic number and necrosis(P＜0.05);Chromosome 17 aneusomy was detected in 8 of 30 patients(26.7%),and was no significant difference with the clinical pathological factors(P＞0.05).(2)In the three types of resistance genes,P-gP and TopoⅡexpression were related with pathological karyokinesis(P＜0.05),also TopoⅡwith the cell type,epithelioid cells expressed was significantly more than the other two types(P＜0.05),and GST-πWith clinicopathological parameters including age,sex,tumor location,cell type,tumor size, mitotic figures and necrosis no significant difference(P＞0.05).Correlation analysis showed that it was a significant positive correlation between P-gP and GST-πexpression(r=0.408,P=0.025),and was negatively correlated between P-gP and TopoⅡexpression(r=-0.530,P=0.003),and was no significant difference between GST-nand TopoⅡexpression(r=0.308,P=0.097).(3)The co-expression rates of p 16 protein deletion with P-gP,GST-πand TopoⅡprotein expression were 40.0%,23.3%,36.7%respectively,as well as p16 gene deletion rate. The positive expression rate of p53 protein was 43.3%(13/30),and was related with pathological karyokines(P＜0.05),and the co-expression rates of p53 protein expression with P-gP,GST-πand TopoⅡprotein were 23.3%,16.7%,20.0%.Conclusions:(1)EGIST exhibited p16 gene deletion and/or chromosome 17 aneusomy like GIST cases.Detection of them with FISH may be useful in predicting prognosis of EGIST.(2) EGIST emerged multidrug resistance which was associated with the deletion of p16 gene and/or p16 protein expression and chromosome 17 aneuploidy change possibly. The deletion of p16 gene and/or p16 protein expression may stimulate reaction of one or more drug resistance gene product(P-gP,GST-πand TopoⅡ) in vivo,so caused the drug-resistant of tumor cells.(3)Some patients with EGIST occurred several resistance genes or drug resistance of antitumor drug mediated by P-gP,GST-πand TopoⅡprotein in tumor cell itself. Tumors of p53-positive expression may be less sensitive to chemotherapy drug.
|
PDF Full Text Request