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Expression CD 44v9 Of In Osteosarcoma,Giant Cell Tumor Of Bone And Osteochondroma

Posted on:2006-08-18Degree:MasterType:Thesis
Country:ChinaCandidate:W GaoFull Text:PDF
GTID:2144360152496929Subject:Surgery
Abstract/Summary:PDF Full Text Request
IntroductionOne of the biological feature of malignant tumor lies in its invasien and telemetastasis , which is believed to be correlated with the change of adherin expression in turner cells weaken the catercelledar attachment makeing turner cells isollated from surrounding worml cells . This is the first step of invasion and metatasis . On the other hand , adherin expressed in tumor cell to vascular endo-theluem, resulting in vasadar meatstasis.Recent years, as the research of molecular biology and tumor genesis develops , it has been known that Clusten of Differentiation (CD44) , as an adhesion molecule, plays an important role in invasion and telemetastasis of malignant tumor.CD44 is a transmembrane glycoprotein and be called ECM - RIII and Hermes least 20 exons and introns which is scattered in exons or their peptide products are designatedCD44v. CD44s is ubiquitously expressed in normal tissues, but CD44v expression is restricted . The functions of CD44 include: cell adhesion, lymphocyte honing and activation, myelopolisis and angiohenesis. Tumor cells express different CD44 involving in tumor growth and metastasis is that it can change cell adhesion and to signal to both the locomotory and mitogenic machinery of the cell. CD44 can also induce the tumor cells to produce autocrine growth factors. CD44 has the ability to take up and degrade hyaluronate and this property could allow tumor cells to detachment. CD44 might also assist in the function of tumorgenesis of other oncogenes such as Ras. The interrelation between CD44 and tumor has been confirmed in many tumors and cell lines. There is little research on the relation of CD44 and normal bone and bone tumor. Whatis less is the study on the expression of CD44v9 in bone tumors with different biological behavior.MaterialsAll samples were taken from the Department of Pathology of Chinese Medical University from 1992 to 2001. The samples are well Preserved in paraffin blocks. Cutting in 5u,m sections. In each the tumor diagnosis was based on his-topathological examination The samples include 26 cases osteosarcoma, 34 cases giant cell tumor of bone (GCTB) (Jaffe I 15 cases, 2 15 cases and 3 4 cases) and 23 cases osteochondroma as control. Monoclonal antibody rat against human CD44v9 was produced by Maxim. Co Fujian.MethodsIn this study, We use a standard S - P immunohistochemical staining procedure to detect the expression of CD44v9 in 20 cases osteosarcoma, 28 cases giant cell tumor of bone and compare to 23 cases osteochondroma. CD44v9 staining is yellow - brown on membrane. We scores 5 high visual random in double - blind way. ( 200) According to the numbers of staining cells, it is divided pos-itiveness and negation. Negative cells ^25% ,we call negation. Positive cells > 25% ,we call positiveness. x2test was used to analyzed the data.Results55. 00% of osteosarcoma expressed CD44v9 and 24. 41% of GCTB expressed CD44v9 None of the samples of osteochondroma was stained. The expression of CD44v9 in osteochondroma is negative. Significant statistical correlation of CD44v9 expression was found in either osteosarcoma of GCTB compared with osteochondroma. Significant statistical correlation of CD44v9 expression was also found in grade 2 - 3 of GCTB compared with grade 1. The difference of CD44v9 expression between osteosarcoma and GCTB is significant. The differ-ence of CD44v9 expression is not significant between osteosarcoma and GCTB e 2 -3.DiscussionCD44 is a transmembrane glycoprotein, encoded on the short arm of chromosome 11. Gene length is 50 Kb, The genetic sequence contains at least 20 exons and introns, which inserted in exons. The genetic squence contains constant and variable exons. According to the type of exon, CD44 molecules can be divided into two groups: the ubiquitously expressed standard isoform (abbreviated to CD44s) and CD44v which molecules containing the variable exons or their peptide products. Variation occurs at the rtanscription stage and the splicing together of exons to form mRNA is called alternative splicing. In theory, alteration splicing would allow more than 1000 different CD44 variant to be generated. By far, more than 10 CD44 isoforms were confirmed. The distribution of CD44v is restricted in normal tissue.The correlation between CD44 and tumor was confirmed by German researchers in 1991. CD44 act on tumor growth, invasion and metastasis mainly because it affects cell adhesion, regulates mitogenic giogenesis. Tumor cells express many different variant CD44 molecules. The expression is tissue specific. CD44v9 is an important CD44 isoform. Many studies have shown the correlation between CD44v9 expression and neoplasm. In colorectal carcinoma, CD44v9 collaborate with p53 and K - ras in tumorgenesis and its expression is previous to that of p53 and K - ras. In non - small - cell lung cancer and ovarian cancer, expression of CD44v9 is correlated closely with tumor growth, invasion and metastasis , which is by the way of vascular or lymphatic system. In soft tissue sarcomas , CD44v9 is associated with a high risk for local recurrence, and correlated with poor survival. Because the products of CD44 are soluble in serum, much more interest in the relation between CD44 level in serum and the tumor is being generated.The studies about bone and bone tumor have shown that CD44 is expressed by cells of osteoblast lineage throughout the osteoblast differentiation sequence.Human MG - 63 osteosarcoma line can also express CD44. But there is difference in expression of CD44 isoforms between osteoblast cell and osteosarcoma cell. The difference can affect cell adhesion and probably has a role in tumor-genesis and tumor invasion. The mechanism of this process maybe as follow: the altered expression of CD44 affects cell adhesion, at the same time, CD44 assist in tumorgenesis with oncogene Ras. CD44 induce the tumor cells to produce au-tocrine growth factors. CD44 is also act on angiogenesis, and accelerate of tumor development. These functions of CD44 are mainly due to CD44v9. In this test, cytoplasmic staining of CD44v9 was observed. According to documents, this cy-toplasmic staining was also accentuated at the infiltrating tumor margin, which would be consistent with the proposed role of CD44 in tumor invasion.In this test, the objects are the nost common malignant bone tumor - osteosarcoma and the osteolytic tumor - GCTB which property is among malignant and benign. Osteochondroma is used as control. CD44v9 expression of all samples was observed. The aim is to detect the function of CD44v9 in bone tumorgenesis and the clinical significance of the expression in diagnosis and treatment. The results have shown that significant statistical correlation of CD44v9 expression was found in either osteosarcoma of GCTB compared with osteochondroma. Significant statistical correlation of CD44v9 expression was also found in grade 2 -3 of GCTB compared with grade 1. The difference of CD44v9 expression between osteosarcoma and GCTB is significant. The results suggest that CD44v9 expression is significant in different malignant level in bone tumor. It can be concluded that CD44v9 is correlative to bone tumor, and can be a supplement parameter for determining malignant level and estimating prognosis in bone tumors.ConclusionThe expression of CD44v9 in osteosarcoma is obviously higher than that of osteochondroma, and the difference is significant. The expression of CD44v9 in GCTB is also obviously higher than that of osteochondroma, and the difference is significant. The difference of CD44v9 expression between osteosarcoma and...
Keywords/Search Tags:CD44v9, Osteosarcoma, Giant cell tumor of bone, Osteochondroma, Immunohistochemistry
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