EB virus latent membrane protein (LMP1) and expression of survivin in nasopharyngeal carcinoma
【Abstract】 Objective To investigate the nasopharyngeal squamous cell carcinoma of EB virus latent membrane protein LMP1, and survivin expression and prognosis. Methods The
immunohistochemical SP method, 83 cases of nasopharyngeal squamous cell carcinoma of the organizations LMP1 and survivin tags, analyzed the clinical stage, radiation therapy within three years after the results of relationship. The results of
LMP1 expression and clinical stage (P> 0.05), but relapse within three years after radiotherapy (P <0.05). survivin and clinical stage, relapse within three years after radiotherapy (P <0.05). LMP1 and survivin are associated (P <0.05).
Conclusion LMP1 and survivin in nasopharyngeal carcinoma has important prognostic value, can be used for clinical treatment of the reference index.
Key words nasopharyngeal carcinoma LMP1; survivin immunohistochemistry
Expressions of Epstein Barr Virus Latent Membrane Protein
1 (LMP1) and survivin in Nasopharyngeal Carcinoma and their Clinical Significance
Key words: Nasopharyngeal; Carcinoma; LMP1; survivin; Immunohistochemical method
NPC (Nasopharyngeal carcinoma, NPC) is a common malignant tumor in China, particularly Guangdong and Guangxi areas of high-fat, with the gradual in-depth on the NPC study, EBV
infection and is closely related to people's NPC has been recognized. survivin is an inhibitor of apoptosis, studies
have shown that the degree of survivin expression in stage of disease progress and the extent of malignant tumor tissue is consistent. We used immunohistochemistry to detect NPC in
poorly differentiated squamous cell carcinoma of the most
common pathological tissues and survivin expression of LMP1, combined with clinical stage, three years after radiotherapy for recurrence of such information as to whether the study to explore both in the NPC the role of the relationship and its significance.
1 Materials and methods
83 cases of nasopharyngeal carcinoma specimens were from our hospital in January 1998 ~ January 2002 close examination of the paraffin-embedded tissues.
NPC clinical stages of nasopharyngeal carcinoma according to the National Conference, Fuzhou in 1992, recommended standards , the 28 patients with stage ? ~ ?, ? period
of 26 cases, ? period 29 patients were divided into three groups; by radiotherapy would be cases of relapse within three
years whether the were divided into 48 cases without recurrence group and recurrence of group two sets of 35 cases.
1.3 Immunohistochemical detection method
Using peroxidase labeled streptavidin staining S P
method. Using an antibody were purchased in the United States Santa Cruz company's products, using the work of the concentration of antibodies: mouse anti-human monoclonal
antibody LMP1 1:80, rabbit polyclonal antibody anti-human
survivin 1:100, SP kit purchased from Beijing Zhongshan
Company, the entire process carried out according to kit instructions. With phosphate buffer (phosphatic buffered saline, PBS) instead of a resistance as negative control.
LMP1 in cancer cells cytoplasm, membrane yellow-brown
granules, survivin in cancer cell nuclei and cytoplasm yellow-
brown granules, the number of positive cells "of 5% positive mark.
1.5 Statistical analysis
Using SPSS11.5 software, χ2 test. PEMS3.0 software,
correlation analysis. P <0.05 significant differences.
2.1LMP1 and survivin in nasopharyngeal carcinoma in different clinical stages of expression groups
(1) LMP1 in ? ~ ? stage cases, 28 cases of negative
expression shown in Figure 1, expression shown in Figure 2, the positive rate is higher than in stage ? case group, below
the case group stage ?. However, LMP1 in different stages of the positive rates showed no significant difference. (2)
survivin in ? ~ ? stage cases, 28 cases of negative
expression shown in Figure 3, positive expression shown in Figure 4, the positive rate of less than the case group stage ? and ? case group, ? ~ ? Phase The positive rate of stage ? Group, ? stage group was statistically significant positive rates, ? period, ? stage group showed no
significant difference in positive rates in Table 1. Table 1 LMP1, survivin expression and clinical stages of NPC poorly differentiated squamous cell carcinoma of the relationship
between the Note: LMP1 in the group stage ? ~ ? and stage ?
positive rate of positive rate of a comparison: χ2 = 0.0593,
P = 0.08075; ? ~ ? Phase Group stage ? positive rate and
positive rate of a comparison: χ2 = 0.0128, P = 0.9101; ?
period The positive rate of stage ? a comparison group: χ2 =
0.1271, P = 0.7215. survivin in the group stage ? ~ ? and
stage ? positive rate of positive rate of a comparison: χ2 =
6.4803, P = 0.0109; ? ~ ? stage group the positive rate and positive rate of stage ? a comparison: χ2 = 7.9875, P =
0.0047; ? period The positive rate of stage ? a comparison
group: χ2 = 0.0458, P = 0.83052.2LMP1 three years after radiotherapy without recurrence of the case group than in the positive rate of recurrent cases within three years after
radiotherapy group, in comparison with there are statistically significant. survivin in the three years after radiotherapy without recurrence of the cases positive rate of less than three years after radiotherapy for recurrence of the disease
group, in comparison with statistical significance, Table 2. Table 2LMP1, survivin expression and recurrence after radiotherapy for three years whether the relationship between
the Note: LMP1 three years after the radiotherapy group and no recurrence after radiotherapy positive rate and positive rate of recurrence within three years of comparison: χ2 = 5.3989,
P = 0.0201. survivin in the radiotherapy group and no recurrence three years after the positive rate of recurrence within three years after the radiotherapy group comparison of positive rates: χ2 = 7.4532, P = 0.0063. 2.3LMP1 with
survivin expression in nasopharyngeal carcinoma in the relationship between the Table 3 the two between factors statistically significant correlation. Expression and survivin
expression in Table 3LMP1 Note: LMP1 and Survivin correlation between the two factors: r = 0.4960, P = 0.0000
Apoptosis in cancer research has always been a hot issue, its occurrence in tumor development, treatment, etc. have
played an important role. LMP1 is the EB virus latent infection is an important transformation of the expression of membrane proteins, was identified as having cancer gene functions of proteins. Kawanish , Komano , Souza  and other study found that LMP1 can inhibit H1299 epithelium, B cells, Burkitt's lymphoma cells and apoptosis in Jurkat cells and so on. survivin was found in a 1997 apoptosis inhibitor, belongs to a family of apoptosis inhibitory protein (IAPs), because in the embryonic tissues and most tumors showed high expression, while the normal tissues and cancer tissues did not express, so attention [5,6]. Reposted elsewhere in the paper for free download http://
LMP1 expression and clinical stage of the relationship between the rarely reported in this set of experiments in Table 1 shows the different stages group shows no significant difference in expression of LMP1 is no obvious link with the staging of nasopharyngeal carcinoma. survivin expression in stage ? ~ ? group and the group stage ?, ? stage group
there were significant differences in sex, ? stage group, ?
period in the group expression was significantly higher than that in group of stage ? ~ ?, ? Stage ? phase group and
between the two groups without significant differences in sex,
and Qi Wei Wei  and others reported survivin in stage ? ~
? NPC tissues positive rate of 33%, ? ~ ? period 79.2% were
similar, indicating the survivin with nasopharyngeal carcinoma is closely related to clinical staging. Radiation treatment of
tumors is mainly through direct physical effects (necrosis) and induce gene expression in cells (apoptosis) to promote tumor cell death, in which tumors induce tumor cell apoptosis is an important mechanism in radiation therapy . Activation of Caspase 3 is a terminal effector of apoptosis, once activated, the cells enter the irreversible stage of apoptosis. Radiation-activated apoptosis of tumor cells NFκB
antagonist may be related to c IAP2 expression and
activation of C rel [9,10]. Fa-Qing Tang et al  with
the experimental verification of the LMP1 could activate NFκB
involved in nasopharyngeal carcinoma cells, radiation therapy-
induced apoptosis antagonist. Table 2 shows that this group LMP1 expression and recurrence within three years after radiotherapy the prognosis is closely related to, LMP1 expression of who may be prompted to poor prognosis. This is evident from clinical validation of the Fa-Qing Tang et al
 were the possibility of experimental results. survivin can directly act on Caspase, the main inhibiting Caspase 3,
Caspase 7 activity, blocking the apoptosis process can also be indirect through p21 inhibition Caspase, to prevent
apoptosis , Asanuma et al  using quantitative RT
PCR detection of survivin mRNA expression of survivin expression was found in inverse proportion to the sensitivity of radiation therapy, survivin expression inhibits radiation-
induced Caspase Activation; inhibiting expression of survivin mRNA can increase the sensitivity of radiation therapy. Table 2 shows that this group survivin expression and recurrence within three years after radiation therapy is closely related to clinical cases of analysis results with previous experimental results, survivin expression was prompted to radiotherapy is ineffective, poor prognosis. The LMP1, survivin if there is both relevant link? Access to the domestic related literature, there are hair-Qing Tang et al
 proposed EB virus LMP1 through activation of NFκB, AP1
increase survivin expression. With the NFκB inhibitor IκB
dominant negative mutants and AP 1 (c Jun) dominant
negative mutants inhibit NFκB and AP1 activation,
respectively, can be blocked by LMP1 increases survivin expression. Table 3 shows, LMP1 and survivin, statistically significant correlation to the clinical analysis of cases verified by two related factors.
Through this analysis, we have reason to believe that,
LMP1, survivin these two factors can be used as prognostic
indicators for nasopharyngeal carcinoma, suggesting that LMP1, survivin as a cancer treatment may be molecular targets for improving therapy of tumors in experimental radiation exposure basis, to become a new cancer treatment breakthrough.
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