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Study On Clinicopathological Characteristics And Metastasis-associated Molecular Mechanisms Of Malignant Fibrous Histiocytoma

Posted on:2011-01-16Degree:MasterType:Thesis
Country:ChinaCandidate:X C BanFull Text:PDF
GTID:2154360308968256Subject:Pathology and pathophysiology
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ObjectiveThe aim of the present study was to observe clinicopathologic characteristics of patients with MFH, analyse the impact factors for metastasis and prognosis; to explore the relevant molecular mechanisms of MFH metastasis, so as to assess the metastatic potential and prognosis of MFH.Methods1. During January 1989 to January 2007,121 cases with MFH were collected to analyse clinicopathologic characteristics and the correlation between clinicopathologic factors and metastasis, prognosis.2. Using 66 patients and their clinicopathologic data above, Immunohistochemical staining were performed on the slides to study the expression of CXCR4,SDF-1,PGK1,MMP7,CathepsinD to explore their role in the metastastic process of MFH.3. During January 2003 to September 2009, frozen specimens of 20 cases were collected, the mRNA expression of CXCR4, SDF-1, PGK1, MMP7, CathepsinD were evaluated by Real-time PCR analysis, for further study of their role in MFH metastastic process.Results1. Clinicopathologic features of 121 MFH cases and analysis of metastasis, prognosis(1)Analysis of Clinicopathological features of 121 MFH cases showed, lower extremity commonly occured, accounting for 53.72%; the maximum diameter of primary tumor was 8.24cm; pleomorphic of Histological type was the majority, accounting for 86.00%; local recurrence rate was 55.40%; lymph node metastasis was 2.48%, hematogenous metastasis rate was about 30.58%, of which lung metastasis percent was 37.50%, combined metastasis percent was 25.00%, lung, bone, liver and combined metastasis percent were 80.00%; the median survival time was 47.02 months,1,3,5-year cumulative survival rate was 74.00%,49.00%, 44.00%.(2)Analysis of clinicopathological parameters and patients' metastasis, prognosis showed that patients with tumor diameter≥5cm, location in retroperitoneal and abdominal cavity, marginal resection, radiotherapy were more prone to distant metastasis (P<0.05); Univariate analysis showed that, cumulative survival rate of patients with Male, occurred in retroperitoneal and abdominal cavity, marginal resection, tumor largest diameter≥5cm, distant metastasis were lower compared with the control groups(P<0.05); Multivariate analysis showed, factors associated with death were tumor size (RR=2.740, P=0.005) and distant metastasis (RR=5.219, P=0.000).2 Preliminary study on metastasis-associated molecular mechanisms of MFH(1)In the primary tumors of MFH with metastasis, protein and mRNA expression of CXCR4, SDF-1 were significantly higher compared with those without metastasis (P<0.05), protein expression of CXCR4 was positively associated with SDF-1(rs=0.514, P<0.05),5-year cumulative survival rate with protein co-overexpression of CXCR4 and SDF-1 was significantly lower compared with control group (P<0.05).(2) In the primary tumors of MFH with metastasis, protein and mRNA expression of PGKl were significantly higher compared with those without metastasis (P<0.05), protein expression of CXCR4 was positively associated with PGK1 (rs=0.514, P<0.05),5-year cumulative survival rate with protein co-overexpression of CXCR4 and PGK1 was significantly lower compared with control group (P<0.05).(3) In the primary tumors of MFH with metastasis, protein and mRNA expression of MMP7, CathepsinD was significantly higher compared with those without metastasis (P<0.05),5-year cumulative survival rate with protein overexpression of MMP7 was significantly lower compared with control group (P<0.05).Conclusions 1. Tumor size, location and resection correlated with metastasis of MFH; Tumor size and metastasis are independent prognostic factors for MFH.2. Overexpression of CXCR4/SDF-1 in primary tumor with metastasis may promote distant metastasis of MFH3. PGK1 may indirectly promote distant metastasis of MFH through interaction with CXCR4/SDF-1.4. Substrate degradation of MMP7, CathepsinD may be involved in distant metastasis.of MFH mediated by CXCR4/SDF-1.5. High expression of CXCR4, SDF-1, PGK1 in primary tumor of patients with MFH may be associated with poor prognosis.
Keywords/Search Tags:MFH, Chemokine Receptors and Ligand, Glycolytic Enzymes, Metastasis, Prognosis
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