The Expression Of NF-κBp65、HIF-1α、MMP-9and Their Correlations With Angiogenesis In Extranodal NK/T Cell Lymphoma, Nasal Type

Objective:The extranodal NK/T cell lymphoma, nasal type (EN-NK/T-NT) clinical manifestation is complicated, the prognosis is related to many factors. Most of the EN-NK/T-NT express resistance genes, chemical therapy, effect is not very effective, survival time short, poor prognosis, has become a hot spot of scientific research in recent years. The aim of this study was to assess the relationship between the expression of the NF-icBp65, HIF-la, MMP-9and the tumor angiogenesis in EN-NK/T-NT, to provide new reference for biological characteristics, clinical diagnosis and treatment schemes for EN-NK/T-NT.Methods:Specimens of EN-NK/T-NT were obtained from42patients between July2007and July2010in the department of otorhinolaryngology head and neck surgery of the first affiliated hospital, Zhengzhou University. There were27males and15females in the group of EN-NK/T-NT, ages from17to76years old (mean48years).32cases of the nasal cavity,5cases of the nasopharynx,1cases of the hart palate,1cases of the soft palate,3cases of the tonsil. The specimens of control group derived from the nasal mucosa of the inferior turbinates of15adults. The cases were stained with immunohistochemical SP method. The monoclonal antibodies were used to detect the expression of NF-κBp65, HIF-1α and MMP-9potein, and anti-CD34monoclonal anibodies were used to label MVD. Statistical analysis was executed by SPSS17.0statistical package. P value of less than0.05was considered significant.Results:1The expression of CD34in EN-NK/T-NT tissues and turbinate mucosa tissues.The capillaries in EN-NK/T-NT was increased and with the vessel lumina dilated. MVD in EN-NK/T-NT tissues and turbinate mucosa tissues was41.4±6.2, and22.5±3.6, respectively. There was also significantly different between two groups(t=11.267, P<0.01).2The expression of NF-KBp65protein in EN-NK/T-NT tissues and turbinate mucosa tissues.The positive rate of NF-κBp65in the42cases of EN-NK/T-NT tissues was73.8%(31/42), while that in control20%(3/15). There was a significant difference between two groups (X2=18.321, P<0.01)。3The expression"of HIF-la protein in EN-NK/T-NT tissues and turbinate mucosa tissues.The positive rate of HIF-la in the42cases of EN-NK/T-NT tissues was66.7%(28/42), while that in control13.3%(2/15). There was a significant difference between two groups (X2=13.140, P<0.01).4The expression of MMP-9protein in EN-NK/T-NT tissues and turbinate mucosa tissues.The positive rate of MMP-9in the42cases of EN-NK/T-NT tissues was73.8%(31/42), while that in control13.3%(2/15). There was a significant difference between two groups(X2=16.842, P<0.01).5The correlation analyse of expression of NF-KBp65, HIF-1α, MMP-9and MVD in the EN-NK/T-NT tissues.There existed positive correlation between NF-KBp65, HIF-1α, MMP-9 expression and MVD in EN-NK/T-NT tissues, Moreover, the value of MVD increased with the intensity of NF-κBp65, HIF-1α, MMP-9expression in the EN-NK/T-NT tissues.(r=0.569,0523,0.581, P<0.01)6The correlation analyse of expression of NF-κBp65, HIF-1α and MMP-9in the EN-NK/T-NT tissues.Positive correlation was obverved between the expression of NF-κBp65and HIF-la, NF-κBp65and MMP-9, HIF-la and MMP-9in the EN-NK/T-NT tissues, respectively(r=0.782,0543,0.633, P<0.01)7The correlation analyse of expression of NF-κBp65, HIF-1α, MMP-9and clinical indexes in the EN-NK/T-NT tissues.Positive correlation was between NF-κBp65and MMP-9with Ann Arbor stages (P<0.05), HIF-1α and MVD with vascular invasion (P<0.05), while the positive rates of NF-κBp65, HIF-1α, MMP-9and MVD were not related to the sex, age, LDH, B symptoms, lymph node metastasia, hemoglobin and International prognostic index (IPI)(P>0.05).Conclusion:1The level of NF-icBp65, HIF-1α, MMP-9expression are significantly higher in EN-NK/T-NT tissues than in the control group, NF-KBp65, HIF-1α, MMP-9may play a roal in the development of EN-NK/T-NT.2There exist positive correlation between NF-κBp65, HIF-1α, MMP-9expression and MVD, which suggest that NF-κBp65, HIF-la, MMP-9may promote angiogenesis and lead to the growth of EN-NK/T-NT induce.3Positive correlation between NF-κBp65, HIF-la, MMP-9expression in EN-NK/T-NT tissues suggests that they could co-promote the growth and angiogenesis in EN-NK/T-NT tissues.4Positive correlation was between NF-KBp65and Ann Arbor stages, between HIF-la, MMP-9and vascular invasion, negative result needs more sample size for further study.