Dissertation
Dissertation > Medicine, health > Oncology > Gastrointestinal Cancer > Pancreatic tumors

The Expression of TGF-β1, Smad4 and p27kip1 in Pancreatic Adenocarcinoma and Its Clinical Significance

Author JiHuaQing
Tutor XuZhiLin
School Zhengzhou University
Course Department of Gastroenterology,
Keywords Pancreatic adenocarcinoma TGF-β1 Smad4 p27kipl Immunohistochemistry.
CLC R735.9
Type Master's thesis
Year 2004
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Pancreatic adenocarcinoma is one of the most common malignancy of the digestive tract and in recent years,its incidence rate is increasing. Because it is not easy to find pancreatic cancer at the early stage and most of the cancer cann’t be resected,the five-year surrival rate is less than 5%.Therefore,every effort should be made to research the mechanism of human pancreatic tumorigenesis and develop better methods for early diagnosis. Recent studies showed that the mutations of oncogenes or antioncogenes participated in the occurrence and development of the pancreatic cancer. Of the transforming growth factor- ?(TGF- P )superfamily, TGF-1,plays an important role in cancer progression by functioning both as an antiproliferative factor and as a tumor promoter, hi normal cells, TGF- V 1 acts as a tumor suppressor by inhibiting cellular proliferation or by promoting cellular differentiation or apoptosis.Pancreatic cancer cells lose their TGF- ?-mediated growth inhibition as a result of mutation or loss of expression of the genes for one or more components of the TGF- ?signaling pathway. Meanwhile, secretion and activation of TGF- ?1 by tumor cells also stimulate tumor development and progression by locally inhibiting immune functions.Smad4 is an important component in the TGF- ?familysignaling cascade.lt transduces signals to the nucleus where it regulates transcription of target genes.p27kipl is a member of the universal cyclin-dependent kinase inhibitor(CDKI) family and is regulated by cell contact inhibition and TGF-.The level of p27kipl protein expression decreased during tumor development and progressionJn this paper,immunohistochemical technique (SABC) was applied to detect the expression of TGF-1,Smad4 and p27kipl in specimens of pancreatic carcinoma,pancreatitis and normal pancreatic tissue in order to investigate the possible mechanism of pancreatic carcinogenesis and the clinical significance of them.. Material and methods:1. 42 resected primary pancreatic adenocarcinoma samples, 13 pancreatitis and 12 normal pancreatic specimens which were adjacent to pancreatic carcinoma and confirmed pathologically as normal pancreatic tissue were collected. All the tissues were fixed in 10% neutral formalin and embedded in paraffin.2. SABC immunohistochemical technique was performed for detecting the expression of TGF- ?l,Smad4 and p27kipl in these three kinds of tissues.3. The data were analyzed by software SPSS 10.0. The correlation between TGF- ?l,Smad4 and p27kipl and various clinicopathological features of tumors was analysed by using the X2-test or Fisher’s exact test. A two-side P value of less than 0.05 was considered statistically significant.Result:1. The immunohistochemical staining of TGF- ? mainly located in the cytoplasm.The pattern of staining was diffuse.In 42 spcimens of pancreatic carcinoma,the positive rate of TGF- fl 1 was 69.05 %,higher than that in nomal pancreatic tissue (16.67%)(P<0.05),whereas the positive rate in 12 samples of pancreatitis was 46.15%,compared with that of the tumors,there was no significant difference.Besides,the express of TGF-?1 protein was correlated withclinical stages and lymph node metastasis (p<0.05),but not correlated with tumor cell differentiation(P>.05).2. Smad4 protein was expressed in the nucleus and cytoplasm of pancreatic carcinoma cells with the positive rate of 52.38%.The pattern of staining was focal or diffuse.The positive expressions were 84.62% and 91.67% in pancreatitis and normal tissue respectively.There were significant difference between them and pancreatic cancers (P<0.05).No association was observed between Smad4 expression and clinical parameters of the pancreatic cancer including tumor stage,pathological grade and presence of lymph node metastasis (P>0.05).3. Staining for p27kipl was observed primarily in the nucleus.The positive rate of p27kipl protein in pancreatic carcinoma was 45.24%,lower than that in pancreatitis (P<0.05)’In normal pancreatic tissue,the positive rate was 50%,compared with that of the cancer, there was no

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