Clinicopathological significance of expression of HIF-1αand P-gp in pancreatic carcinoma

摘要

Pancreatic cancer is a malignant neoplasm of thepancreas. The prognosis is poor, with fewer than 5％ of those diagnosed may survivefive years. Complete recovery is still rare. P-Glycoprotein (P-gp) is one of thexenobiotic transport proteins implicated in multidrug resistance in neoplastic tissues,it's integral efflux protein, expressed in some normal tissues which have excretionalfunction Hypoxia inducible factor lalpha (HIF-1α) plays an important role in solidtumor formation and survival by promoting anaerobic metabolism and angiogenesis. OBJECTIVE: To investigate the expression of Hypoxia inducible factor1alpha and P-Glycoprotein in pancreatic carcinoma to determine theirclinicopathological significance and their correlation. METHODS: Paraffin-embedded tissue samples were collected from 34pancreatic carcinoma, 7 chronic pancreatitis and 12 normal pancreas patients, whoreceived surgical resection. We examined the expression of HIF-1α and P-gp byimmunohistochemistry (SP method). The relationship between HIF-1α and P-gpprotein expression and clinicopathological factors was statistically analyzed. RESULTS: The positive staining of HIF-1α was shown brown-yellow in thecytoplasm or nucleus and the positive staining of P-gp was brown-yellow in thecytoplasm with some staining on the cellular membrane. 1. In pancreatic cancer tissue, the positive rate of HIF-1α protein expression was70.50％, in chronic pancreatitis tissue was 28.57％ and in normal pancreas tissue was8.33％. HIF-1α protein expression was significantly higher than that in the chronicpancreatitis tissue and normal pancreas tissues (P < 0.05). 2. In pancreatic cancer tissue, the positive rate of P-gp protein expression was58.82％, in chronic pancreatitis tissue was 14.2g％ and in normal pancreas tissue was8.33％. P-gp protein expression was significantly higher than that in the chronicpancreatitis tissue and normal pancreas tissues (P < 0.05). 3. HIF-1α and P-gp expression in pancreatic cancer tissue were significantlyrelated to tumor stage and lymph node metastasis (P < 0.01), while they were notshows significantly to the age, sex, tumor size, and differentiation grade of tumor (P >0.05). 4. In pancreatic cancer tissue, HIF-1α and P-gp protein expression werepositively correlated (P < 0.05). CONCLUSION: 1. Up-regulated expressions of HIF-1α a and P-gp exist in pancreatic carcinoma, so it can act as a fundamental guide to clinical diagnosis. 2. The expression of HIF-1α and P-gp may participate in the development,progression, invasion metastasis and poor prognosis of pancreatic carcinoma 3 The expression of HIF-1α and P-gp is a positive correlation between them,indicating that there may exist a crosstalk between P-gp signal pathway and HIF-1αsignal pathway, which may act synergistically to promote the progression ofpancreatic carcinoma.

目录

英文文摘

论文说明:LIST OF ABBREVIATIONS

CHAPTER 1 INTRODUCTION

CHAPTER 2 MATERIALS AND METHODS

CHAPTER 3 RESULTS

CHAPTER 4 DISCUSSION

CHAPTER 5 CONCLUSION

CHAPTER 6 REFERENCES

IMAGES

REVIEWER

ACKNOWLEDGEMENTS