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Detection Of Twist, P53 And MDM2 Expressions In The CIN And Cervical Squamous Cell Carcinoma By Manual Tissue Chip

Posted on:2010-03-08Degree:MasterType:Thesis
Country:ChinaCandidate:H R ZhangFull Text:PDF
GTID:2144360275969657Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Objective: Cervical cancer is the most common female malignancy, accounting for female reproductive system for more than half of malignant tumors. It is a serious threat to women's health and life. For the occurrence of cervical cancer mechanisms, domestic and foreign scholars ascendant. It has great significance from the molecular level study of the pathogenesis of cervical cancer for the clinical diagnosis of cervical cancer, differential diagnosis and guide clinical treatment.Twist are present in Drosophila, mouse, human and other biological body of a basic helix-loop-helix(bHLH) transcription factor, mainly expressed in placenta, embryonic and adult mesoderm mesodermal some sources undifferentiated sub-organization. Twist is highly conserved transcription factor, and the key regulators of epithelial - mesenchymal transition process. It has a significant impact in tumor invasion and metastasis.p53 gene is a negative cell cycle regulatory factors, the loss of normal function mutations so that it can lead to tumor formation. p53 gene has an important regulatory role in cells growing as a transcription regulatory factor. Twist with the p53 promoter can an important trans-activator interaction between HOXA5 and regulate its activity. Twist also by reducing the p53 upstream regulator p14ARF expression affected the stability of p53 and p53 can prevent post-translational modification, such as serine phosphorylation, and this modification of p53 activation are indispensable.MDM2 are cloned from one containing murine double minute, the spontaneous transformation of cells BALB/3T3DM, it is a highly amplified, evolutionarily conservative oncogene, can lead to spontaneous tumorigenesis. MDM2 gene amplification can lead to p53 gene inactivation. p53 and MDM2 mutual regulation between in the regulation of cell division and proliferation aspects.This topic using tissue chip technique and immunohistochemical method,detection of different degrees of expression of Twist, p53 and MDM2 in cervical lesions. To analysis of Twist, p53 and MDM2 abnormal expression of in cancer occurrence and development of mutual relations. To investigate interrelations between Twist, p53, MDM2 and clinical indicators of cervical cancer interrelationships.Methods:1 28 cases of normal cervical squamous epithelia, 96 cases of CIN and 44 cases of cervical carcinoma were collected in Hebei Province People's Hospital Pathology in August 2007 -2008 in August. 2 By manual tissue chip technique and immunohistochemistry SP method was used to examine for the expression, relation and the effect of Twist, p53 and MDM2 in cervical carcinoma, CIN and normal cervical squamous epithelia.3 Analysis the data use SPSS13.0, significance was set at P<0.05.Results:1 The result of tissue chip 5 tissue chips(6×5,7×5) were made rquired by the subject. 3 tissue dots were absence, 14 tissue no significant tissue structures. The sample of total is 151 cases, of which cervical squamous cell carcinoma 40 cases, CIN organization 85 cases, 26 cases of normal cervical tissue in finally. The rate of complete tissue dots was 89.88%.The result of haematoxylin-eosin(HE) staining was uniformity, showing the structure is good and no dropping, moving and wrinkling.The immunohistochemical result show that the positive location was accurate and the background was clear.2 The expression of TwistIn CIN and cervical squamous cell carcinoma cases, both the basal layer or other lesions are visible on each floor cells strongly positive expression, in the expression of Twist, cervical squamous cell carcinoma(50.0%) and the level CIN(CINⅢ, 48.3%; CINⅡ, 42.3%; CINⅠ, 10.0%) were significantly higher than those of normal cervical squamous epithelium(0%) (P<0.05). Twist overexpression in cervical squamous cell carcinoma was significantly higher than CINⅠ(P<0.05); it was no significant difference between Cervical cancer and CINⅢ, CINⅡ(P>0.05). the Twist expression between CINⅢ, CINⅡand CINⅠhave no statistically significant differences(P>0.05).3 The expression of p53In normal cervical epithelia the expression of p53 is absence. From normal cervical squamous epithelium(0%), CINⅠ(10.0%), CINⅡ(46.2%), CINⅢ(51.7%) to cervical squamous cell carcinoma(52.5%), p53 positive cells of expression gradually increased. p53 in cervical squamous cell carcinoma and CINⅡ, CINⅢwere higher than in normal cervical squamous cell carcinoma, the difference was significant (P<0.05). CINⅠand cervical squamous cell carcinoma, CINⅢ, CINⅡdifferences were statistically significant(P<0.05). With the increase in expression level, but there was no significant difference among cervical squamous cell carcinoma, CINⅢand CINⅡ(P>0.05).4 The expression of MDM2MDM2 in cervical squamous cell carcinoma strong positive expression(60%), significantly higher than the normal cervical organization(0%). CINⅠ(26.7%), CINⅡ(50%), CINⅢ(56.7%) was significantly higher than the normal cervical organization(0%), the difference was significant(P<0.05). The positive rate of MDM2 difference between cervical squamous cell carcinoma, CINⅢ, CINⅡand CINⅠwas statistical significance(P<0.05). However, in cervical squamous cell carcinoma and CINⅢ, CINⅡbetween the MDM2 expression was no significant difference(P>0.05).5 The relation of Twist,p53,MDM2There was a positive correlation between expression of Twist and p53(P<0.05,r = 0.683),expression of Twist and MDM2(P<0.05,r=0.363),expression of p53 and MDM2(P<0.05, r=0.454).6 The relationship between the expression of Twist,p53,MDM2 and clinical pathological features of cervical carcinoma.No significant relationship were found between the expression of Twist, p53, MDM2 and clinical pathological features(P>0.05).Conclusions:1 Twist, p53 and MDM2 overexpression in CIN and cervical squamous cell carcinoma group were significantly higher than those of normal cervical squamous epithelium, suggesting that Twist, p53 and MDM2 can diagnosis the presence of CIN cervical intraepithelial lesions and squamous cell carcinoma.2 Twist, p53 and MDM2 overexpression in CINⅡ, CINⅢand cervical squamous cell carcinoma group were significantly higher than those of CINⅠ, suggesting that Twist, p53 and MDM2 can help distinguish CINⅠbetween CINⅡ, CINⅢand cervical squamous cell carcinoma, can guide the clinical treatment.3 Cervical squamous cell carcinoma of Twist, p53 and MDM2 protein expression, there is a positive correlation between indicating Twist, p53 and MDM2 protein in the incidence of squamous cell carcinoma of the cervix have a catalytic role, the three have a synergistic effect.4 There is no correlation between Twist, p53 and MDM2 overexpression and other clinical factors,it's shows that these three indicators are no help for prognosis of the role of judge.
Keywords/Search Tags:Cervical squamous cell carcinoma, Cervical intraepithelial neoplasm, Twist, p53, MDM2, Tissue chip Immunohistochemical staining
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