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The Expression And Clinical Significance Of HIF-1a And PTEN In Human Hepatocellular Carcinoma

Posted on:2008-03-03Degree:MasterType:Thesis
Country:ChinaCandidate:J K LiFull Text:PDF
GTID:2144360215488960Subject:Surgery
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Objective: The hepatocellular carcinoma (HCC) is one of the most common malignant tumors in our country, which is associated with high lever of malignancy, poor prognosis. Therefore, to explore the pathogenesy of HCC remain a challenge to modern medical science. The HCC grow quickly, causing tissue oxygen deficiency. In this state, the Multiplication and infiltration of HCC are mainly because of the existing of HIF-1. Hypoxia inducible factor-1α(HIF-1α) is an unique active transcription factor in the specific oxygen deficiency, which expresses commonly in malignant tumors. HIF-1αis essential in activating angiogenesis, anaerobic metabolism, for the proliferation and migration of tumor cells. HIF-1 is adjusted mainly by oxygen deficiency, at the same time ,Anti-oncogene plays an important role and PTEN , as one of the Anti-oncogene, play an important role. So far, PTEN is the first Anti-oncogene which has phosphatase activity, and was paid widespread attention since its discovery. PTEN can negatively accommodate the expression of HIF-1αby P13K/AKT signal path. In our countury, there were many reports about HIF-1 or PTEN and HCC, but no report that detect both of them yet. In our experiment, Immunohistochemistry was used to detect the protein expression of HIF-1αand PTEN in HCC, para-cancerous tissues and normal hepatic tissues. The aim of our experiment was to investigate the protein expression of HIF-1αand PTEN, the role in the occurrence and development of HCC as well as the relationship between HIF-1αand PTEN. It may provide a new therapy in exploring the pathogenesy of the HCC.Methods: Fifty tumor tissue samples and thirty-two tumor-surrounding tissue samples were obtained from primary HCC patients undergoing surgical resection. Twelve normal liver tissue samples were taken from previously patients with benign tumor. Immunohistochemistry was used to detect the expression of HIF-1αand PTEN in HCC, para-cancerous tissues and normal hepatic tissues. We also analyze the relationship between HIF-1αand PTEN. Statistical analysis was used to determine the relationship between their expression and clinicalpathological parameters.Results1 HIF-1αand PTEN protein stain In HCC: HIF-1α-positive stain was observed in forty-five of 50 tumor tissue samples (94%), and PTEN -positive stain in forty (86%). In contrast, HIF-1α-positive stain was only in 17 of 28(60.7%) in tumor-surrounding tissue samples and PTEN-positive stain in 28 (100%). Only one of 12 (8.3%) HIF-1α-positive stain in normal liver tissue samples was observed and PTEN-positive stain in 12 (100%). The express of HIF-1αand PTEN is significant difference between HCC, para-cancerous tissues and normal hepatic tissues (P<0.05).2 The express of HIF-1αand PTEN is significant difference between HCC and para-cancerous tissues in HCC and Para-carcinoma of 27 pairs (P<0.05).3 The expression intensity of HIF-1αin hepatocellular carcinoma assume negative correlation to pathological degree, and positive correlation to vein embolus, size of tumor, intrahepatic or lymphatic metastasis (P<0.05) .The expression intensity of PTEN in hepatocellular carcinoma assume correlation to pathological degree(P<0.05),but has nothing to do with vein embolus, size of tumor, intrahepatic or lymphatic metastasis.4 A significant negative relationship was observed between the expression of HIF-1αand PTEN in HCC(r=-0.292,P=0.04).Conclusions1 The express of HIF-1αand PTEN is significant difference between HCC, paracancerous tissues and normal hepatic tissues, which indicates that HIF-1αand PTEN expression is associated with the occurrence and development of HCC.2 The expression intensity of HIF-1αin hepatocellular carcinoma assume correlation to pathological degree, vein embolus , size of tumor and intrahepatic or lymphatic metastasis, which indicate that HIF-1αplays an important role in activating angiogenesis, tumor growth, the proliferation and migration of tumor cells. The expression intensity of PTEN in hepatocellular carcinoma assumes correlation to pathological degree. The lower HCC is differentiated, the weak expression of PTEN, which indate that PTEN play an important role in promoting the malignant transformation of tumor.3 A significant negative relationship was observed between the expression of HIF-1αand PTEN in HCC, which indicates that anti-oncogene PTEN may inhibit the expression and lower the stability of HIF-1αto negatively regulate the expression of HIF-1α. HIF-1αand PTEN are associated with the occurrence and development, infiltration and metabasis of HCC.4 Observing HIF-1αand PTEN together may be valuable to evaluate the biology behavior, treatment and prognosis of HCC. It is useful to explore the pathogenesy of liver cancer and open up a new treatment method.
Keywords/Search Tags:Hepatocellular Carcinoma, immunohistoch- emistry, HIF-1α, PTEN, Hypoxia, Invasion, Metatastasis
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