HIF-1α和P-gp在胰腺癌中的表达及其临床病理意义

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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.
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