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Expression Of P21~(ras), TGF-α And EGFR In Pancreatic Carcinoma And Its Clinical Value

Posted on:2003-05-16Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhaoFull Text:PDF
GTID:2144360065955729Subject:Digestive medicine
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Pancreatic adenocarcinoma, one of the digestive carcinomas, results in serious problems to human health. Most cases are discovered at late stage when they are not curable by surgery due to lack of typically clinical symptoms and sensitive detecting methods. The five-year survival rate is barely one to 5%. As other tumors, the mechanism of pancreatic carcinogenesis has not been cleared. Recent studies showed that aberrant activation of signaling pathways are strongly related to the occurrence and development of cancers. p21ras protein acts as a transducer in the signaling pathways. TGF- a , a mitogenic peptide that is structurally and functionally related to EOF, can also bind to EGFR and subsequently activate the tyrosine kinase existing in EGFR internal domain , and at last, promote DNAsynthesis and the proliferation of tumor cells. In order to investigate the possible mechanism of pancreatic carcinogenesis and the clinical value of p21ras, TGF- a and EGFR expression in pancreatic carcinoma, an immuhistochemical Streptavidin-Peroxidases (SP) method was used to examine the expression of the three kinds of proteins.Material and Methods: (1) 30 surgically resected primary pancreatic ductal adenocarcinoma samples and 10 normal pancreatic tissue samples which were adjacent to pancreatic carcinoma but were confirmed pathologically as normal pancreatic tissue as well as 60 other digestive carcinoma samples including 20 hepatocellular carcinoma, 20 cholangiocarcinoma and 20 colorectal carcinoma samples were collected. All the tissues were fixed in 10% neutral formalin and embedded in paraffin. (2) SP immunohistochemical method was performed on formalin-fixed paraffin samples for the detection of p21ras, TGF- a and EGFR. (3) The data were analyzed by software SPSS 10.0, x2-test or exact probability-test was used to compare difference between groups and Spearman grade correlation test was used to analyze the correlation between TGF- a and EGFR . a =0.05 was considered as level of a test.Results: (1) In pancreatic carcinoma, the immunohistochemical staining of p21ras protein was not even and mainly located in the cytoplasm with the positive rate of 63.3%. In normal pancreatic tissue, the positive rate of p21ras protein was only 10.0%. p21ras protein expression was found to be siginificantly elevated in the pancreatic carcinoma compared with normal pancreatic tissue (P<0.05). According to histological grade of pancreatic carcinoma, 30 cases of pancreatic carcinoma were divided into well-differentiated group and poorly-differentiated group. The positive rates of p21ras expression in these two groups were 76.2% and 33.3% respectively. There were significant differences (P<0.05) of the expression of p21ras between the two groups. p21ras protein expression was significantly (P<0.05) higher in the stage I-II than in the stage III- IV with the positive rates of 87.5% and 35.7% respectively. In the group with lymph node metastasis and the group without lymph node metastasis, the positive rates of p21ras were 38.5% and 82.4% respectively. There were significant differences (PO.05) of the expression of p21ras between the two groups. In hepatocellular carcinoma group, cholangiocarcinoma group and colorectal carcinoma group, thepositive rates of p21ras protein expression were 60.0%, 0 and 50.0% respectively. No significant differences (P>0.05) were found between the pancreatic carcinoma group and hepatocellular carcinoma group as well as pancreatic carcinoma group and colorectal carcinoma group. There were significant differences (P<0.05) when comparison was made between pancreatic carcinoma group and cholangiocarcinoma group. (2) Positive staining of TGF- a was mainly located in the cytoplasm and/or in the nucleus of pancreatic carcinoma cells with the positive rate of 80.0%. In the normal pancreatic tissue, the positive rate of TGF- a was 20.0%. There were significant differences (P<0.05) when comparison was made between pancreatic carcinoma group and normal pancreatic tissue group. The positive rate of TGF- a in...
Keywords/Search Tags:primary pancreatic ductal adenocarcinoma, p21ras, TGF-α, EGFR, immunohistochemisty
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