The Expression Of HMGB1 And RAGE Protein In Cervical Squamous Cell Carcinoma And Clinical Study

OBJECTIVE To investigate the expression of the high mobility group boxl(HM GB1)and the receptor of advanced glycatl on end-products(RAGE)in human cervical squamous cell carcinoma(CSCC)and to explore the relationship of HMGB1 and RAGE expression to the differentiation degree,size,invasion and metastasis of CSCC,to study the relationship between HMGB1 and RAGE in the development of the CSCC.METHOD Immunohistochemical staining of tissue microarrays and Western blot analysis were conducted to detect the expression of HMGB1 and RAGE in the following tissue samples:30 carcinoma in situ,90 invasive CSCC without metastasis, 30 invasive CSCC with metastasis,30 cases of normal cervical squamous epithelia.RESULTS HMGB1 mainly located in cytoblast.RAGE maily located in cytoplasm.1)The positive-expression rate of HMGB1 was 58.7%(88/150)in CSCC,the positive-expression rate was16.7%in normal cervical squamous epithelia,the difference was significant P＜0.01.The positive-expression rate of HMGB1 in CSCC with lymph node states and in which not were 83.3%and 52.2%, respectively,the difference was significant P＜0.01.The positive-expression rate of HMGB1 in CSCC with invasion and in cancer in situ and in normal cervical squamous epithelia were 61.7%,46.7%,16.7%,respectively,the difference was significant P＜0.01.The positive-expression rate of HMGB1 in CSCC of FIGO stageⅠ,Ⅱwere 53.9%,79.5%,respectively,the difference was significant P＜0.01. The positive-expression rate of HMGB1 was correlated with tumor development, size,invasion and metastasis of CSCC(respectively,P＜0.01),but had no relationship with the degree of differentiation(P＞0.05).2)The positive-expression rate of RAGE was 48.0%(72/150)in CSCC,The positive-expression rate was 13.3%in normal cervical squamous epithelia,the difference was significant P＜0.01.The positive-expression rate of RAGE in CSCC with lymph node states and in which not were 73.3%and 43.3%,respectively,the difference was significant P＜0.01.The positive-expression rate of RAGE in CSCC with invasion and in cancer in situ and in normal cervical squamous epithelia were 50.8%,36.7%,13.3%,respectively,the difference was significant P＜0.01.The positive-expression rate of RAGE in CSCC of FIGO stageⅠ,Ⅱwere 42.1%,65.9%,respectively,the difference was significant P＜0.05.The positive-expression rate of RAGE was correlated with tumor development, invasion and metastasis of CSCC(respectively,P＜0.01),but had no relationship with the degree of differentiation and tumor size(P＞0.05).3)The expression of RAGE was positively associated with HMGB1(r=0.508, P＜0.001).4)Western Blot analysis were consistent with immunohistochemical analysis.The positive-expression rate of HMGB1 in CSCC with lymph node states was higher than in which not and normal cervical squamous epithelia,the difference was significant P＜0.01.CONCLUSION The over-expression of HMGB 1 and RAGE is related to the genesis or development or metastasis of CSCC and might be a useful parameter as an indication of tumor invasion,metastasis,prognosis and overall biological behavior of human CSCC,as well as a noval target site for gene therapy.