| Lung cancer with poorest prognosis is the largest threaten to people's health and life. The incidence and mortality of it is increasing most fast in our country. Invasive and metastasis are the primary cause of treatment failure and death in lung cancer. Two of the essential processes require for metastasis are tumor cell invasive of basement membranes (BM) and extracellular matrix (ECM) and tumor angiogenesis. Mammalian heparanase gene was successful cloned in 1999. And it was identified in a variety of malignant tumors, and closely associated withtumor invasion and metastasis. The biological functions of this enzyme in vivo were degradation of ECM and BM, release and activation heparin-binding growth factors such as basement membrane (bFGF) and vascular endothelial growth factor (VEGF) from heparan sulfate proteoglycans (HSPG), and induce angiogenesis. Tumor angiogenesis were morphological basis for tumor growth and metastasis. VEGF is a growth factor with stronger angiogenic potent and the highest specificity. It has the ability to increase microvascular permeability and provide tumor with nutrition before angiogensis. Since then, VEGF gene express was identified in many kinds of tumors, and associated with tumor metastasis and relapse. To our knowledge, expression of heparanase and its biological role in connection with VEGF expression in non-small cell lung cancer (NSCLC) has not been evaluated so far. This study detects heparanase mRNA and VEGF expression in NSCLC by immuno-histochemistry and reverse transcription polymerase chain reaction (RT-PCR) test to explore the clinicopathological significance of heparanase gene and VEGF expression in NSCLC, evaluates the role of heparanase and VEGF and their correlationship involved in NSCLC invasion and metastasis and provides theory basis for antiheparanase therapy and antiangiogenesis therapy in lung cancer at molecular level.Materials and methods: Sixty-five samples were obtained from patients undergoing lung resection in Henna Chest Hospital from May 2000 to October 2001. All samples were divided into two part, one was kept in liquid nitrogen, and the other was fixed in 10% neutral buffered formalin and embedded in paraffin, then continuously sliced for 3 times at Sum thick, 2 for immuohistochemic test, 1 for hematoxylinesoin stain. None of the patients had received preoperative chemo-or radio- therapy. All cases were confirmed histologically. (l)Lung cancer: 65cases, 45 males, 20 females; age ranged from 32 to 76 years (52.3+7.9, means+SD); 44 cases with squamous cell cancer, 21 with adenocarcinoma; 6 cases in stage I a 7 cases in stage I b, 11 in stageIIa, 13 cases in stage lib, 10 cases in stagellla, 6 cases in stagelllb and 12 cases in stageIV; 17 cases were in low differentiation, 29 cases in moderate differentiation and 19 in high differentiation. (2) control group: 14 males, 6 females; age ranged from 28 to 72 years (48.5 + 6.7, mean+SD); 4 cases were with pulmonary cyst, 3 with bronchiectasis, 9 with pulmonary tuberculosis, 2 with pulmonary inflammatory, 1 with pulmonary hamartoma, 1 with lung abscess. Expression of heparanase mRNA was examined by reverse transcription PCR, and VEGF was detected by labeled streptavidin biotin method. Statistical comparisons for significance between nominalvariables were evaluated by Fisher's exact Test, correlation analysis were evaluated by Attest.Results: (1) The expression of heparanase mRNA in NSCLC was significantly higher than in benign pulmonary diseases (P<0.01).(2) The expression of heparanase mRNA was higher in cases with lymph node invasive than those without lymph node invasive (P<0.01). In metastasis cases, it was significantly higher than in non- metastasis cases (P<0.01). It was higher in stagelll and stagelVthan in stage I and stage II (P<0.05). The expression of heparanase mRNA was also higher in low differentiation cases than in higher and moderate differentiation cases (P<0.01). In adenocarcinoma it was higher than in squamous cell cancer (P<0.05). It was a...
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