Probing Into The Relationships Between MVD And NF-κB Subtypes, MVD And MBD In Spinal Multiple Myeloma

Background:Plasma cell myeloma is a malignant tumor derived from B-cell line, which is often eroded by Ig secreted by malignant plasma cells, and eventually causes bone corrosion. Plasma cell myeloma is mainly classified into two categories:solitary myeloma and multiple myeloma. Plenty of the preclinical and clinical data have proved the importance of angiogenesis in Plasma cell myeloma. Nuclear factor-κB is also playing a significant role in the occurrence and development of Plasma cell myeloma. Myeloma bone disease occurs insidiously, doing great harm to patients'living quality. Now there are few reports about the relationship among angiogenesis, NF-κB subtypes and myeloma bone disease.Objective:We detected the expression of MVD which is marked by CD34, NF-κB subtypes p50,p65,p52,c-rel,relB and the bone-disease related factors Rankl and Opg in plasma cell myeloma and associated with clinical imaging data. Our aim was to study and research systematically the correlations between MVD and NF-κB subtypes, the correlations between MVD and myeloma bone disease. We also probed into the relationships between these factors and biological behaviors of plasma cell myeloma and screened the prognostic factors of plasma cell myeloma.Methods:A total of 63 cases of spinal PCM underwent operation in Shanghai Changzheng Hospital from Jan.1998 to June 2009 with complete clinical and follow up data involved in this study. The expression of MVD marked by CD34, NF-κB subtypes p50,p65,p52,c-rel,relB and the bone-disease related factors Rankl and Opg were detected on the formalin-fixed paraffin-imbedding tissues by immunohistochemistry. Bone disease ranking was according to the clinical imaging data. The SPSS statistical software were used in analyses on relationship between each factor expression and biological behavior of spinal PCM. The significance of gene expression and survival period was determined by Kaplan Meier survival analyses and Log-Rank test, meanwhile the prognostic factors should be screened.Results:Significant correlation was found between low positive expression and high positive expression of NF-κB p50, with regard to MVD (P<0.05). MVD expressed higher in the group of high-positive expression of NF-κB p50. No significant correlation was found in MVD of the subtypes of NF-κBp65, p52, c-rel and relB. Significant correlation of MVD was found between the degrees of myeloma bone disease (P<0.05). MVD expressed higher in the group of higher bone-disease degree. In spinal PCM, the positive expression rate of the NF-kB subtypes were detected as 82.54% in p50,90.48% in p52, 87.3% in p65,93.65% in c-rel,87.3% in relB respectively, which expressed higher than in normal bone marrow, showing significance (P<0.05). The expression of MVD were detected as 236.02±90.9 on average, much higher than in normal bone marrow,which was 49.3±7.3 on average. And significance was showed in MVD between spinal PCM and the normal bone marrow. (P<0.05). The positive expression rate of the bone disease related factor Rankl were detected as 100%, which expressed much higher than in normal bone marrow. Compared to Rank1, Opg was detected as 15.83% positive in PCM, which expressed lower than in the normal bone marrow, showing significance (P<0.05). Rankl was also correlated with bone disease ranking(P<0.05). The higher the bone-disease degree was, the higher rate Rankl expressed. No other clinical features were related with bone disease ranking (P<0.05). Bone disease ranking was correlated with clinical typing(P<0.05). The bone-disease ranking was higher in multiple myeloma than in solitary myeloma. MVD, bone disease ranking, pathology ranking, clinical typing, age were all correlated with survival time. With the bone-disese-ranking ascending, survival time decreased. The mean survival time of the bone-disese-level is:Ⅲ≤Ⅱ≤Ⅰ. Survival time of the lower pathology levels (ⅠandⅡ)were longer than the higher pathology level(Ⅲ). Mean survival time of multiple myeloma is lower than solitary myeloma. The older group(≥50 years old) lived shorter than the young group(<50 years old).The other clinical agents were not correlated with survival time in spinal PCM(P<0.05).Conclusion:MVD was correlated with the expression degree of NF-κBp50. MVD expressed high while NF-κBp50 expressed high. It meaned that, in clinical therapies, NF-KBp50 could be a target towards angiogenesis in spinal PCM. MVD which was correlated with the progression of bone disease, could be a potential target for treating MBD. The balance of NF-κB and its ligand Rankl/Opg system was disturbed, NF-κB subtypes p50, p52, p65, c-rel, relB and Rankl expressed high intensity and Opg expressed low intensity in spinal PCM. Rank1 had positive correlation with bone disease ranking. Clinical typing could predict the development of the myeloma bone disease, and multiple myeloma developed into the more serious bone disease. MVD, bone-disease ranking, pathology ranking, age and clinical typing could be the prognostic agents of spinal PCM.