HIF-1α和P-gp在胰腺癌中的表达及其临床病理意义

摘要

BACKGROUND:Pancreatic cancer is a malignant neoplasm of the pancreas. The prognosis is poor，with fewer than 5％of those diagnosed may survive five years. Complete recovery is still rare. P-Glycoprotein (P-gp) is one of the xenobiotic transport proteins implicated in multidrug resistance in neoplastic tissues，it’s integral efflux protein，expressed in some normal tissues which have excretional function. Hypoxia inducible factor 1 alpha (HIF-lα) plays an important role in solid tumor formation and survival by promoting anaerobic metabolism and angiogenesis.OBJECTIVE:To investigate the expression of Hypoxia inducible factor 1 alpha and P-Glycoprotein in pancreatic carcinoma，to determine their clinicopathological significance and their correlation.METHODS:Paraffin-embedded tissue samples were collected from 34 pancreatic carcinoma,7 chronic pancreatitis and 12 normal pancreas patients，who received surgical resection. We examined the expression of HIF-1αand P-gp by immunohistochemistry (SP method). The relationship between HIF-la and P-gp protein expression and clinicopathological factors was statistically analyzed.RESULTS:The positive staining of HIF-la was shown brown-yellow in the cytoplasm or nucleus and the positive staining of P-gp was brown-yellow in the cytoplasm with some staining on the cellular membrane.1. In pancreatic cancer tissue，the positive rate of HIF-1αprotein expression was 70.50%，in chronic pancreatitis tissue was 28.57% and in normal pancreas tissue was 8.33%. HIF-la protein expression was significantly higher than that in the chronic pancreatitis tissue and normal pancreas tissues (P＜0.05).2. In pancreatic cancer tissue，the positive rate of P-gp protein expression was 58.82%，in chronic pancreatitis tissue was 14.29% and in normal pancreas tissue was 8.33%. P-gp protein expression was significantly higher than that in the chronic pancreatitis tissue and normal pancreas tissues (P＜0.05). 3. HIF-la and P-gp expression in pancreatic cancer tissue were significantly related to tumor stage and lymph node metastasis (P＜0.01)，while they were not shows significantly to the age，sex，tumor size，and differentiation grade of tumor (P＞0.05).4. In pancreatic cancer tissue，HIF-1αand P-gp protein expression were positively correlated(P＜0.05).CONCLUSION:1. Up-regulated expressions of HIF-1 a and P-gp exist in pancreatic carcinoma，so it can act as a fundamental guide to clinical diagnosis.2. The expression of HIF-1 a and P-gp may participate in the development，progression，invasion，metastasis and poor prognosis of pancreatic carcinoma.3. The expression of HIF-1 a and P-gp is a positive correlation between them，indicating that there may exist a crosstalk between P-gp signal pathway and HIF-la signal pathway，which may act synergistically to promote the progression of pancreatic carcinoma.

目录

ABSTRACT

TABLEOFCONTENTS

LIST OF ABBREVIATIONS

CHAPTER 1 INTRODUCTION

CHAPTER 2 MATERIALS AND METHODS

2.1 Patients and specimens

2.2 The main reagents and Instruments

2.3 Slices produced

2.4 Immunohistochemistry

2.5 Scoring criteria

2.6 Statistical analysis

CHAPTER 3 RESULTS

CHAPTER 4 DISCUSSION

CHAPTER 5 CONCLUSION

CHAPTER 6 REFERENCES

FIGURES

REVIEW

REFERENCES

ACKNOWLEDGEMENTS