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The Effect of HIF-1α and VEGF Protein Expression and Relationship to Biologic Behavior in Oral Squamous Cell Carcinoma

Author: CaiXiaoPan
Tutor: WuYang
School: Second Military Medical University
Course: Clinical Stomatology
Keywords: Oral squamous cell carcinoma HIF-1α VEGF Lymph node metastasis Relapse Biological behavior Prognosis
CLC: R739.8
Type: Master's thesis
Year: 2010
Downloads: 56
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Abstract


Background of oral squamous cell carcinoma (Oral squamous cell carcinoma, OSCC) accounts for about 90% of all oral cancer tend infiltrative growth, and the easy recurrence and neck lymph node metastasis. The reason may be related to the oral tissue blood vessels, lymphatic vessels, muscle near the nerve fibers and other factors, but the molecular biological mechanisms are not yet clear. Development of OSCC The occurrence is a multi-step, multi-gene interaction results. In recent years, attention associated with OSCC biological behavior of a variety of biological indicators. In fact, to rely solely on traditional clinical and pathological factors is difficult to accurately judge the clinical biological behavior in OSCC and different reasons for the same parts, the same clinical stage prognosis is less clear. Thus, finding that accurately reflects the OSCC prognostic characteristics of the biological behavior of indicators is very important. Research purposes using epidemiological methods oral squamous cell carcinoma clinical and pathological features of HIF-1α, VEGF, p53. Of p21WAF1, MDM2 Ki-67 gene expression and OSCCI clinical and biological characteristics relationship. Research methods. Retrospective analysis of clinical and pathological data of 55 cases of OSCC patients Changzheng Hospital, Second Military Medical University in January 2001 - May 2008 dentistry admitted. Grouping: based on OSCC predilection is divided into lip cancer (8 cases), Tongue cancer (15 cases), the base of the tongue cancer (11 cases), buccal cancer (10 cases), gingival cancer (11 cases) group; according to the preoperative 1:1 ratio without lymph node metastasis, and 24 cases of cervical lymph node metastasis, cervical lymph node metastasis in 31 cases (lip cancer no transfer cases); selected cases, follow-up, follow-up time after 5 to 98 month, which lost to the six cases, 49 cases of a valid clinical observation of cases. In the prognostic evaluation of the experimental definition of local recurrence or neck lymph node metastasis and poor prognosis. Clinical data analysis methods: the diseased parts, preoperative lymph node metastasis, gender, age, tumor grade, postoperative local recurrence with lymph node metastasis epidemiological analysis; statistical methods: hierarchical data using the chi-square test; using Kaplan-Meier survival analysis method and Logrank test for univariate analysis, recurrence rate were calculated after 1-5 years. 2 the immunohistochemical EnVisionTM method to detect the expression of HIF-1αVEGF. P53, p21WAF1, MDM2, Ki-67 protein in OSCC, pathology film reading, qualitative analysis of gene expression, immunohistochemistry results using two scoring law, according to the staining intensity and the number of positive cells scoring average (Mean score, MS) quantitative analysis of the different parts of OSCC different degree of differentiation, lymph node metastasis, preoperative different prognosis gene protein expression differences. Statistical methods: According to the results of the test of homogeneity of variance, respectively, using a completely random rank sum test (Kruskal Wallis Test) and the Mann-Whitney test or single-factor analysis of variance (One-way ANOVA). 3 6 gene protein expression levels of qualitative and quantitative data the indicator cluster analysis (the Variables clustering analysis), while Pearson or Spearman correlation analysis of gene expression, screening related gene; further analysis of HIF screened -lα, VEGF gene expression and its correlation with OSCC differentiation, metastasis, prognosis and biological behavior indicators of relationship to study the expression of multiple genes in OSCC clinical significance. Results 1. Analysis of clinical data of 49 cases of OSCC cases, well differentiated in 27 cases, 22 cases in poorly differentiated; OSCC, the overall local recurrence, lymph node metastasis was 38.6%, recurrence rate various parts: the base of the tongue up to 54.5% , the gingival of 45.5%, 37.5% of buccal cancer, 35.7% of the Sheqian Ministry lip cancer was 0.0%; preoperative lymph node metastasis, tumor histological grade have a significant impact on the prognosis of preoperative lymph node metastasis recurrence metastasis rate was 56.5%, higher than that without lymph node metastasis (23.1%) (P lt; 0.05), poorly differentiated group of metastasis and recurrence rate was 54.5%, higher than the well-differentiated group (25.9%) (P lt; 0.05); cervical lymph node metastasis in poorly differentiated merger preoperative, postoperative recurrence rate as high as 83.3%, exponentially higher than other groups of recurrence and metastasis rate (P lt; 0.05): differentiation of OSCC prognosis with age no significant gender relations; KaPlan-Meier survival analysis method, 1-5 years after the recurrence rate, recurrence or metastasis occurs mainly in the first two years after surgery. 2 HIF-1a, VEGF, p53 of p21WAF1, MDM2 Ki-67 protein expression 2.1 HIF-1a protein expression positive rate was 69.1%, the positive rate of VEGF protein expression in 40% of p53 was 78.2%, MDM2 to 85.5%, P21WAF1 96.4%, Ki-67 was 83.6%. 2.2 of HIF-1A Expression of significant difference (P LT; 0.05); expression level of HIF-1a in the gingival cancer other parts OSCC 2-9 times the level of expression between the different onset portion. 2.3 VEGF expression in tongue cancer and gum cancer, their expression levels may be associated with lymph node metastasis of OSCC poor prognosis group VEGF expression than the good prognosis group, but not statistically significant; VEGF expression in gingival cancer level is positively correlated with poorly differentiated. HIF-1a, VEGF gene synergy with OSCC biological behavior of the correlation analysis results through indicators clustering analysis found that HIF-1α, VEGF clustered into one group, p53, Ki-67 of p21WAF1 a class, MDM2 alone as a class; 55 cases of OSCC HIF-1α, VEGF protein expression was positively correlated, r = 0.3 (P lt; 0.05). Further analysis found that HIF-1α, VEGF expression and OSCC preoperative lymph node metastasis, positive relationship, especially with tongue cancer, buccal cancer lymph node metastasis; positively correlated with OSCC in poorly differentiated; with the front of the tongue, cheek, gums the significant positive correlation between poor prognosis; less than or equal to 55 years of age group, male group were positively correlated. Tongue cancer in terms of HIF-1α, high expression of VEGF Tongue cancer lymph node metastasis in poorly differentiated highly correlated, the correlation coefficient greater than 0.95, but at the base of the tongue cancer HIF-1α, VEGF high expression lymph node metastasis may be relevant, but not statistically significant in this group, and its expression has nothing to do with the degree of differentiation. HIF-1α, VEGF expression with well-differentiated group, preoperative lymph node metastasis, and poor prognosis group, female group gt; 55 age group related to sex (P gt; 0.05). Conclusion cervical lymph node metastasis in poorly differentiated unfavorable prognosis of oral squamous cell carcinoma, especially in poorly differentiated OSCC shift, poor prognosis (metastasis and recurrence rate of 83.3%), lymph nodes of the neck lymph node transfer or (and) in poorly differentiated OSCC patients should strengthen the follow-up, especially after surgery the previous two years. We believe that the co-expression of HIF-1α, VEGF and OSCC preoperative lymph node metastasis, poorly differentiated, prognosis, especially in the narrow sense, oral cancer, this relationship is more pronounced. Both might be able to clinical diagnosis, treatment, new research direction.

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CLC: > Medicine, health > Oncology > Oral cavity, maxillofacial tumors
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