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Expression and Significance of Leptin and Matrix Metalloproteinase-2 in Gastric Carcinoma

Author: HouXiaoXu
Tutor: DongZiMing;XueChangGui
School: Zhengzhou University
Course: Pathology and pathophysiology
Keywords: Gastric cancer leptin MMP-2 Immunohistochemistry
CLC: R735.2
Type: Master's thesis
Year: 2007
Downloads: 68
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Abstract


Cancer is one of the background and purpose of gastric cancer is a serious threat to people's lives and health, morbidity ranks first in the digestive tract tumors, ranking fourth of all tumors, the mortality rate of all malignant tumors. About 2/3 of patients with gastric cancer were residents of developing countries, which accounted for 42% in China. Of tumor invasion and metastasis are two problems in the clinical treatment, that is, most patients lethal factor. Therefore, how to improve the rate of early diagnosis of gastric cancer and monitoring their invasion and metastasis scholars concern. Leptin (leptin) is a product of the obese gene encoding, mainly secreted by adipose tissue, play an important role in regulating food intake, energy metabolism, and to maintain the weight balance. Recent studies of leptin can inhibit apoptosis of tumor cells, promoting their proliferation and increase the capacity of its invasion of the basement membrane and promote angiogenesis is closely related to the development of many malignancies. About the role of leptin in gastric cancer and evolution are not yet see the depth. Matrix metalloproteinase - 2 (matrix metalloproteinase-2, MMP-2) is one of the members of the MMP family, not only has the collagenase activity involved in extracellular matrix (extracellular matrix, ECM) the dissolution, but also has the function to promote tumor angiogenesis in the tumor growth, and plays an important role in the transfer process. Studies have shown that, leptin can upregulate the expression of MMP-2, both may play a synergistic role in gastric cancer development. To this end the present study, immunohistochemical methods, detection of leptin and MMP-2 protein expression in different stages of gastric lesions, aims to explore the role of both gastric cancer invasion and metastasis and their relationship , to provide for the early diagnosis of gastric cancer, the prevention and treatment and prognosis of new theoretical foundation. MATERIALS AND METHODS 1.57 cases of gastric biopsy specimens and 60 patients with gastric cancer specimens archived paraffin blocks from the Department of Pathology, the First Affiliated Hospital of Zhengzhou University, from 1998 to 2004, 19 cases of normal gastric mucosa, chronic atrophic gastritis with intestinal metaplasia the 19 cases, 19 cases of atypical hyperplasia, 15 cases of early gastric cancer, advanced gastric cancer, 45 cases, all specimens were confirmed by pathology. After 10% formalin-fixed, dehydrated and embedded in paraffin. 2. Application the immunohistochemistry SP (Streptavidin peroxidase) assay leptin and MMP-2 protein in normal gastric mucosa, chronic atrophic gastritis with intestinal metaplasia, dysplasia, early gastric cancer and advanced gastric cancer tissue expression. 3. For statistical analysis the experimental data SSPS10.0 statistical package, respectively, χ ~ 2 test, Spearman correlation analysis, α = 0.05 level of inspection. Results 1. The leptin protein positive staining located in the cytoplasm, a small amount of interstitial visible positive expression. leptin protein in normal gastric mucosa, chronic atrophic gastritis with intestinal metaplasia, dysplasia, early gastric cancer and advanced gastric cancer tissue positive expression rates were 21.1%, 36.8%, 47.4%, 53.3% and 84.4%, respectively. Leptin protein positive expression rate of advanced gastric cancer tissue were significantly higher than in normal gastric mucosa, chronic atrophic gastritis with intestinal metaplasia, atypical hyperplasia and early gastric cancer (P <0.05). 60 cases of gastric cancer specimens, leptin invading the serosa group, 89.3% (25/28), the protein expression was significantly higher than serosal invasion group, 65.6% (21/32) (P <0.05), lymph node metastasis 88.2% (30/34), significantly higher than those without lymph node metastasis was 61.5% (16/26) (P <0.05), according to the TNM staging, leptin protein in Ⅲ Ⅳ group expression of 90.9% (30/33) higher than that in Ⅰ Ⅱ group 59.3% (16/27) (P <0.01), regardless of the degree of differentiation of leptin protein expression in gastric cancer (P> 0.05). 2. MMP-2 protein positive staining also localized in the cytoplasm. MMP-2 protein in normal gastric mucosa, chronic atrophic gastritis with intestinal metaplasia, dysplasia, early gastric cancer and advanced gastric carcinoma, the positive expression rate of 5.3%, 21.1%, 36.8%, 53.3% and 80.0%, MMP-2 protein expression in advanced gastric carcinoma rates were significantly higher than in normal gastric mucosa, chronic atrophic gastritis with intestinal metaplasia, atypical hyperplasia and early gastric cancer (P <0.05), early gastric cancer group compared with normal group differences was statistically significant (P <0.01). Serosal invasion group, 89.3% (25/28), the MMP-2 protein expression was significantly higher than serosal invasion group, 59.4% (19/32) (P <0.01), lymph node metastasis was 85.3% (29 / 34) was significantly higher than those without lymph node metastasis was 57.7% (15/26) (P <0.05), according to the TNM staging, MMP-2 protein expression in stage Ⅲ Ⅳ group rate 87.9% (29/33) High Ⅰ Phase Ⅱ group 55.6% (15/27) (P <0.01), regardless of the degree of differentiation of MMP-2 protein expression in gastric cancer (P> 0.05). 3.60 cases of gastric cancer tissues, leptin, and a common positive expression of MMP-2 in 36 cases, common negative expression of the six cases, the Spearman correlation analysis showed r_s = 0.663 (P <0.01), leptin and of MMP-2 The expression of the existence of a significant positive correlation. Conclusion 1. The leptin protein showed an increasing trend in the process of gastric cancer, and the expression level of lymph node metastasis, invasion depth and clinical stage clinical pathological biological behavior, suggesting that high expression of the leptin protein involved in the occurrence and development of gastric cancer. 2. MMP-2 protein expression was significantly increased in gastric carcinoma with lymph node metastasis, infiltration depth and clinical stage clinical and pathological biological behavior, suggesting that high expression of MMP-2 may be involved in the development of gastric carcinogenesis and enhanced gastric invasiveness. 3. leptin protein and MMP-2 protein expression was significantly positively correlated, suggesting that some kind of regulation of relations between the two, and the synergies involved in gastric carcinogenesis and evolution process. 4. leptin protein and MMP-2 protein in gastric carcinogenesis, development, invasion and metastasis, suggesting that the expression of the Joint Monitoring both as gastric cancer, the indicator of the degree of progress and prognosis.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Gastric neoplasms
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