Expression Of Survivin, NF-KB And VEGF In Laryngeal Squamous Cell Carcinoma

BACKGROUNDThe complex molecular mechanisms in malignant transformation and progression of tumor have still not been well understood yet. With the rapid development of tumor molecular biology it has been demonstrated that neoplasm formation was a molecular incidence involved in multiple factors with multiple procedures, which was participated in by multiple oncogenes and anti-oncogenes. Laryngeal squamous cell carcinoma (LSCC) is the most common malignant neoplasm in otolaryngology and increasing incidence has been observed in recent years. The pathogenesis and pathologic mechanism involved in LSCC are still unclear, neither is therapeutic response be improved significantly. New findings show that the occurrence and progress of LSCC are correlated with excessive proliferation and apoptosis reduction of cells. To explore the pathogenesis and pathologic mechanism of LSCC and to seek new therapeutic methods of LSCC are of momentous significances.As a new member of inhibitor of apoptosis (IAP), Survivin is a tumor specific anti-apoptosis factor that is expressed selectively in all the most common human carcinomas but not in normal adult tissues.Survivin has bifunction of inhibiting apoptosis and involving in cell cycle control, expressing in a cell cycle-dependent manner, it directly inhibits Caspase-3 and Caspase-7 activity. During tumor genesis, Survivin expression is inversely correlated with apoptosis and is positively correlated with proliferation. Survivin also participates in angiogenesis. Because it has high specificity, high expression rates in cancer tissue and closed relationship with drug resistance in rumor's chemotherapy and radiotherapy, Survivin has attracted enormous attention. Survivin is an potential target gene in gene therapy. Researches focused on knocking down its expression to inhibit the growth of tumor and improve the sensitivity to radio therapy and chemotherapy. Studies indicated that Survivin played a crucial role in the genesis and progression of malignancy. Survivin has been used as a novel diagnostic/therapeutic target in cancer. Survivin has been a hot spot in the study of nowadays.Nuclear factor-kappa B (NF-KB)is one of the factors play multiple and important roles in many cells. It has bifunction of inhibiting apoptosis and involving in cell cycle control. NF-KB suppresses apoptosis by inducing expression of a number of genes whose products inhibit apoptosis, including inhibitors of apoptosis (IAPs), several members of the Bcl-2 family and so on. These anti-apoptotic proteins have been found to work in a coordinated fashion to block apoptosis at multiple steps along the apoptotic cascade or to regulate other pro or anti-apoptotic pathways.Angiogenesis, the formation of blood vessels, is a vital process in tumor growth, invasion and metastasis. Vascular endothelial growth factor (VEGF) and their families all play important role in tumor angiogenesis, and significant anti-tumor effect can be achieved by inhibiting the expression/activity of VEGF or by blocking its down-stream signal pathways.VEGF is, thus, considered to be an important therapeutic target in anti-antigenic cancer therapy strategies.Survivin, NF-KB, VEGF ,they all play important roles in inhibiting apoptosis and involving in cell cycle control .They may work in a coordinated step about the pathogenesis and pathologic mechanism involved in LSCC .So far ,there is no report on the correlations of Survivin, NF-KB, VEGF in laryngeal carcinoma.ObjectiveTo investigate the expression of Survivin and its relationship with the expression of NF-KB, VEGF in laryngeal squamous cell carcinoma (LSCC) and to analyze their correlations with the occurrence and development of LSCC.MethodsThe expressions of Survivin,NF-KB and VEGF in tissues of 57 cases,9 cases of vocal cord polyp(VCP),10 cases of normal mucosa of larynx tissues,7 cases of margins of LSCC were studied by Immunohistochemical technique(S-P) to analyze their correlations with the occurrence and development of LSCC.The data was analyzed by SPSS13.0 software package, x~2test and Fisher's exact test involved. Statistically significant level was considered as "alpha equals 0.05". Results1 Expression of Survivin: Immunoreactivity for Survivin was located at the cytoplasm in LSCC.①The positive expression rates of Survivin in LSCC tissues of 57 cases,9 cases of vocal cord polyp(VCP),margins of LSCC and normal mucosa of larynx tissues cases were 66.67%,0,0,and 0respectively .Comparing the staining rate among those 4 groups, there were significant difference .The positive rates of LSCC was significantly higher than those of 3 groups (P<0.05) .②The positive expression rates of Survivin in III-IV phase and I-II phase were 83.87% and 46.15% respectively. There was significant difference between them (P<0.05) .③The positive expression rates of Survivin in LSCC with I, and II III were 54.54% and 83.33% respectively .There were significant difference between the positive rates of grade I and II, III (P<0.05) .④Survivin was associated with metastasis of Laryngeal carcinoma (P<0.05) .⑤There were significant difference of Survivin positive rates between NF-KB(+) and NF-KB(-).There were significant difference of Survivin positive rates between VEGF(+) and VEGF(-) (P<0.05) .2 Expression of NF-KB: Immunoreactivity for NF-KB was located at the cytoplasm in LSCC.①The positive expression rates of NF-KB in LSCC tissues of 57 cases,9 cases of vocal cord polyp(VCP),margins of LSCC and normal mucosa of larynx tissues cases were 64.91%,0,0 and 0 respectively. Comparing the staining rate among those 4 groups, there were significant difference .The positive expression rates of LSCC was significantly higher than those of 3 groups. (P<0.05) .②The positive expression rates of NF-KB in III-IV phase and I-II phase were 74.2% and 46.2% respectively. There were significant differences between them (P<0.05) .③The positive expression rates of NF-KB were not clearly associated between grade I and II, III (P>0.05) .④NF-KB was associated with metastasis of Laryngeal carcinoma (P<0.05) .⑤There were significant difference of NF-KB positive rates between VEGF (+) and VEGF(-) (P<0.05) .3 Expression of VEGF: Immunoreactivity for VEGF was located at the cytoplasm in LSCC.①The positive expression rates of VEGF in LSCC tissues of 57 cases,9 cases of vocal cord polyp(VCP),margins of LSCC and normal mucosa of larynx tissues were 75.43%,33.33%,28.57%and 0 respectively. Comparing the staining rate among those4 groups, there were significant difference .The positive expression rates of LSCC was significantly higher than those of 3 groups (P<0.05) .②The positive expression rates of VEGF in III-IV phase and I-II phase were 90.32% and 57.69% respectively .There were significant difference between them (P<0.05) .③The positive expression rates of VEGF in LSCC with I, and II III were 63.63% and 91.66% respectively .There were significant difference between the positive rates of grade I and II, III (P<0.05) .④VEGF was associated with metastasis of Laryngeal carcinoma (P<0.05) .CONCLUSION1 The expressions of Survivin,NF-KB and VEGF in LSCC tissues were higher than those in normal mucosa of laryngeal cavity. The expressions of the three marks in LSCC with the metastasis of lymph nodes were higher than those without metastasis. Significant correlation between Survivin/NF-KB / VEGF expression and T-stage.2 Expression of VEGF was positively related to expression of Survivin.3 Expression of NF-KB was positively related to expression of Survivin. NF-KBsuppresses apoptosis by inducing expression of Survivin.4 Expression of NF-KB was positively related to expression of VEGF.5 The high expression of three genes suggest that they play important roles in the formation and metastasis of LSCC.Survivin,NF-KB and VEGF may be identified as a new therapeutic target. NF-KB, VEGF may have a synergic role with Survivin in pathogenesis and progression of LSCC.6 United detection of the expressions of Survivin, NF-KB and VEGF contributes to the diagnosis, therapeutics and prognostic assessment of LSCC.