| Background and aim: Gastric carcinoma(GC) is one of the most common malignant neoplasm in the world, and its carcinogenesis and progression is a procedure involved of multigence and multiprocedure. The fact that no significant improvements exit in the overall outcome for the patients with gastric carcinoma in recent years is mainly deuced to its recurrence , invasion and metastasis. Invasion into surrounding tissues is a prominent phenotype of cancer cells. Regulatory mechanisms of cell motility is undoubtedly critical in this process.The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interaction and of cell-associated protease systems ,which destroy the extracellular matrix(ECM),in order to enable the invading cells to simultaneoudly grip and destroy the anatomical barriers that control cell spreading. The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase linked to signaling events between cells and the extracellular matrix. FAK regulates multiple cellular processes including growth,differentiation,adhesion,motility,and apoptosis,and is overexpressed in a variety of human solid tumors.The urokinase-type plasminogen activator(uPA) system plays a central role in control of cell surface proteolysis and extracellular matrix degradation. The uPA system has been implicated in the progression,metadtasis,and angiogenesis of numerous solid tumors. Nm23-HI(non-metastasis 23-H1) has beenproved to be an inhibiting factor of metastasis in certain human tumors. The nm23 protein has been implicated in a wide variety of biological processes, including suppression of metastasis, proliferation, development, and regulation of differentiation. Although several studies have demonstrated that the expression of FAK,uPA and nm23-Hl are involved into the procedure of carcinogenesis and progression of many kinds of neoplasms, but the relation between their and gastric carcinoma and significance remained controversial. The purpose of this study is to evaluate the role of FAK,uPA and nm23-Hl in carcinogenesis and progression of gastric carcinoma ,in order to clarify the plausible mechanisms of carcinogenesis and progression ,while may provides theoretic foundations for potential new therapy methods of gastric carcinoma.Materials and methods: 60 cases of gastric carcinoma specimens were collected in department of general surgery, the first affiliated hospital of Zhengzhou University from 1997 to 2000.22 cases of adjacent normal gastric mucosa specimens were obtained from the sites >5 cm apart from the primary tumors,includinglO cases normal gastric mucosa, 16 cases dysplasia.46 cases the metastatic nodules were collected. All tissues were identified by pathologist, and were fixed in neutral 10% formaldehyde, and embedded in paraffin. Immunohisochemical streptavidin peroxides conjugate metholdwas used to analyze the expression of FAK,uPA as well as nm23-Hl in normal gastric mucoma(NGM), dysplasia and gastric carcinoma. Data were performed with SPSS 10.0 software. Chi-square test and fisher' exact test of probabilities were used, and Statistically significant level was considered as "alpha equals 0.05".Results:1. Expression of FAK: (1) FAK expression was located in both the cytoplasm and the cytoplasmic membrane of the tumor cells,and interstitium was negative.(2) 0 % (0 / 10) normal mucosa, 25.0% (4 / 16) dysplasia, and 65.8% (46 / 60) gastric carcinoma specimens showed FAK positive stained in the cytoplasms. In gastric carcinoma specimens, the intensity of FAK expression was remarkably increased compared with matched normal mucosa specimens and dysplasia (p<0.05).. (3) WhenFAK expression was compared with clinicopathological features, in 60cases cancer tissues divided into invasion serosal stratum or without invasion serosal stratum group and deep or full stratum group, the authors found that the deeper the extent of tumor infiltration, the higher the FAK expression (P<0.05).Tumors with lymph node metastases had more FAK protein than those without me... |
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