Investigation Of Imaging Features And Molecular Expression Patterns In Prognosis Of GCTB Recurrence

Predicting local recurrence through tumour characteristics in preoperative imaging features PURPOSE: To evaluate the role of tumour characteristics in predicting local recurrence of giant cell tumour of bone(GCTB)by assessing the preoperative imaging features of GCTB.METHODS: Fifty-six consecutive GCTBs in the proximal tibia and distal femur treated with curettage were prospectively enrolled.Patients were grouped in terms of their imaging features on radiography,computed tomography(CT)and magnetic resonance imaging(MRI).All patients were followed up for at least two years after surgery.The correlations between preoperative imaging features and local recurrence were investigated.Imaging features were retrospectively studied by correlation analysis.The differences between rates were tested by the Chi-square and Fisher exact tests;independent factors were determined by multivariate logistic regression analysis.RESULTS: Forty-eight out of fifty-six(85.71%)patients were successfully followed up.Twenty-one patients(43.75%)were diagnosed with recurrent GCTB.Cystic change and adjacent soft tissue invasion were associated with a higher rate of local recurrence compared to the negative groups(P<0.05).Cystic change was identified as an independent risk factor for local recurrence of GCTB(P<0.05).Expansibility was correlated with the “soap bubble” sign and the fluid–fluid level(P<0.05);the “soap bubble” sign was correlated with osteosclerosis and the fluid–fluid level(P < 0.05);cortical bone involvement was correlated with adjacent soft tissue invasion(P<0.05);and cystic change was correlated with the fluid–fluid level(P<0.05).CONCLUSION: Cystic change was an independent risk factor for local recurrence of GCTB.Adjacent soft tissue invasion might indirectly relate to local relapse.A cluster of association relationships between imaging features was revealed,and was helpful to bring more insight into imaging features of GCTB.Imaging features of tumor border in predicting local recurrence of GCTB and correlation analysis with pathologyPUR POSES: We investigated preoperative imaging features on the border of GCTB to determine risk factors of local recurrence.METHODS: Fifty-eight patients with GC TB in proximal tibia or distal femur were enrolled prospectively.GCTBs were grouped in term of various preoperative imaging features.All the patients were treated with intralesional procedures and then followed up for at least two years.Additionally,two cases were enrolled only for pathological basis of specific imaging features.The associations between preoperative imaging features,prognosis and demographic factors were analyzed.The differences between rates were tested by Chi-square test or Fisher exact test,independent factors were determined by multivariate logistic regression analysis.RESULTS: Fifty-three patients were followed up successfully,of which twenty-two patients(41.51%)relapsed during the follow-up period.GCTBs with “paint brush borders” sign and GCTB in proximal tibia had a higher rate of local recurrence(P<0.05).“Paint brush borders” sign on preoperative MR was identified as an independent risk factor for local recurrence(P<0.05).Pathologically,“paint brush borders” sign showed a correlation with local invasion of bone.Females were associated with significant edema(P<0.05);“paint brush borders” sign were more common in proximal tibia compared with distal femur(P<0.05).Of twenty-one cases showed "paint brush borders" sign,patients diagnosed with “paint brush borders” signs on axial,sagittal and coronal planes were 4(19.05%),20(95.24%)and 14(66.67%),respectively.All “paint brush borders” signs could be detected by T1 WI,whereas only 4 cases showed “paint brush borders” sign on T2 WI.CONCLUSION: "Paint brush borders" sign is revealed as an independent risk factor for local recurrence of GCTB.Sagittal T1 WI is crucial for preoperative MR examination to diagnose “paint brush borders” sign.Careful preoperative evaluation of MR images might be helpful to raise surgeons' awareness about the risk of penetrating irregular margins and guide surgical treatment to reduce local recurre nce of GCTB.The value of association between immunohistochemistry and MRI features in prognosis of GCTB recurrencePUR POSES: To investigate the expressions of proteins associated with cystic changes and the "paint brush borders" sign in giant cell tumour of bone(GCTB),and exploring its value in predicting local recurrence of GC TB through correlating with preoperative MR features.METHODS: We investigated the expressions of matrix metalloproteinase-9(MMP-9),vascular endothelial growth factor(VEGF),receptor activator of nuclear factor-? B(RANK),and RANK ligand(RANKL)in GC TBs by immunohistochemical staining,and correlated them with preoperative magnetic resonance imaging(MRI)features.MRI features were retrospectively examined by correlation analysis with gross pathologic sections.The differences between rates were tested by C hi-square test or Fisher exact test.RESULTS: A total of 36 consecutive GCTBs in the proximal tibia or distal femur were investigated.The expression of MMP-9 was associated with cystic changes and the "paint brush borders" sign(P<0.05),and the expression of MMP-9 showed positive correlations with expression of RANKL and VEGF,(P<0.05).Pathologically,the “paint brush borders” sign was investigated and revealed as indicative of local invasion of bone.CONCLUSION: The over expression of MMP-9 played a key role in local recurrence of GC TB,and provided more insights into these preoperative MRI features and molecular expression patterns.Investigation of crosstalk between Notch and RANK pathwaysPUR POSES: Notch and RANK pathways play an important role in progression and bone resorption of GCTB.We aim to investigate the crosstalk between both pathways.METHODS: Quantitative RT-PCR and Western blotting analysis were used to determine the expressions of m RNAs and proteins in mouse osteoclast precursor cell line RAW264.7.Si RNA transfection was used to inhibit the expression of molecular of signaling pathways.The data was analyzed statistically by t-test methods.The differences between rates were tested by C hi-square test or Fisher exact test.RESULTS: RT-PCR showed m RNAs of RANK,Notch1,Jagged1,Jagged2,DLL-1 and DLL-3 were expressed in RAW264.7 cells.The protein expressions of Notch1,DLL-1 and DLL-3 were detected by western blotting analysis,and after si RN A transfection,their m RNA expressions were suppressed by 71%,53% and 70%,respectively.The expression of RANK was up-regulated after Notch1 inhibition.Notch1,Jagged1,Jagged2 were down-regulated while DLL3 was up-regulated after RANKL stimulation.The stimulation also caused down regulations of HES1 and HEY1.CONCLUSION: Our data indicate a potentially positive feedback mechanism between Notch and RANK pathways via interaction with Notch1,it might play a key role in aggressive behaviour of bone resorption in GCTB.Notch1 might be a novel therapeutic target for GCTB.