【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 (P0.05).
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).
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.