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The Expression And Significance Of SDF-1/CXCR4 Biologicalaxis And HIF-1α In Laryngeal Squamous Cell Carcinoma And Lymph Node Metastasise

Posted on:2011-12-02Degree:MasterType:Thesis
Country:ChinaCandidate:L ZhangFull Text:PDF
GTID:2154360308474118Subject:Otorhinolaryngology
Abstract/Summary:PDF Full Text Request
Objective: The carcinoma of larynx is very common malignant neoplasm in otolaryngology and head and neck surgery. And the laryngeal squamous cell carcinoma ( LSCC ) is one of the most common case. The laryngeal carcinoma may be affected by numerous factors, such as stromal cell derived factor-1, SDF-1 which is belong to CXC, kind of Chemokines.Integration of elements (fusin) or CXCR4 for SDF-1 receptor, both specific binding can activate multiple signaling pathways, thereby affecting the transfer and the invasion in laryngeal carcinoma. The hypoxia-inducible factor-1α(HIF-1α) in the two play a synergistic role in the process of influence. In our study, our aim is to investigate some mechanism of SDF- 1, CXCR4 and HIF-1αsignal during the development, migration, invasion and lymph node metastasis of laryngeal cancer. By observing the expression the three indexes in laryngocarcinoma, para-carcinoma, normal laryngeal mucosa and lymph node tissue. And also to find out the associatively relationship between SDF-1/CXCR4 and HIF-1αin laryngeal arcinoma, which will be helpful to find a new cure for laryngeal carcinoma.Methods:1 The expression of SDF-1, CXCR4 and HIF-1αwas detected by immuno - histochemical SP in 40 cases of laryngeal carcinoma tissue and cervical lymph node tissue, 20 cases of para-carcinoma and 19 cases of normal tissue.2 Flow Cytometrye (FCM) for 19 cases of normal tissue, 40 cases of laryngeal carcinoma tissue and cervical lymph node tissue to detect the content of the three indexes.3 SPSS 13.0 was applied to analyze the results of experiment. P≤0.05 indicating significant difference. P≤0.01 indicating very significant difference.Results:1 The expression of SDF-1 protein1.1 The results detected by IHC: The expression of SDF-1 in laryngo carcinoma, para-carcinoma, normal laryngeal mucosa tissues and cervical lymph node tissue by S-P immunohistochemical methods. The expression of SDF-1 in laryngocarcinoma, para-carcinoma and normal laryngeal mucosa tissues is falling down, there is statistic significance (P<0.01). The expression of SDF-1 in laryngocarcinoma is obviously higher than those in para-carcinoma (P<0.01) and in normal laryngeal mucosa (P<0.01) tissues respectively. No significant difference was found between the expression of para-carcinoma and normal laryngeal mucosa tissues (P>0.05). Expression of SDF-1 was correlated with lymph node metastasis (P<0.01), clinical stage (P<0.01) and pathological grading of tumor(P<0.05), but that wasn't correlated with patients'clinical classification, tumor size, smoking history, patients'age and sex (P>0.05). The positive expression rate of SDF-1 protein in metastasis lymph node tissue (88.24%) is higher than those in nonmetastasis lymph node tissue (8.70%), there is statistic significance (P<0.01).1.2 The results detected by FCM: The quantitative expression of SDF-1 protein (FI) in laryngeal carcinoma tissues, para- carcinoma and normal laryngeal mucosa tissues respectively is falling down, there is statistic significance (P<0.01). The quantitative expression of SDF-1 protein in laryngeal carcinoma tissues is obviously higher than those in para-carcinoma (P<0.01) and in normal laryngeal mucosa (P<0.01) tissues respectively. No significant difference was found between the expression of para-carcinoma and normal laryngeal mucosa tissues (P>0.05). Expression of SDF-1 was correlated with lymph node metastasis (P <0.01), clinical stage (P<0.05) and pathological grading of tumor(P<0.05), but that wasn't correlated with patients'clinical classification, tumor size, smoking history, patients'age and sex (P>0.05).2 The expression of CXCR4 protein2.1 The results detected by IHC: he expression of CXCR4 in laryngo carcinoma, para-carcinoma, normal laryngeal mucosa tissues and cervical lymph node tissue by S-P immunohistochemical methods. The expression of CXCR4 in laryngocarcinoma, para-carcinoma and normal laryngeal mucosa tissues is falling down, there is statistic significance (P<0.01). The expression of CXCR4 in laryngocarcinoma is obviously higher than those in para-carcinoma (P<0.01) and in normal laryngeal mucosa (P<0.01) tissues respectively. No significant difference was found between the expression of para-carcinoma and normal laryngeal mucosa tissues (P>0.05). Expression of CXCR4 was correlated with lymph node metastasis (P<0.01), clinical stage (P<0.01) and pathological grading of tumor (P<0.05), but that wasn't correlated with patients'clinical classification, tumor size, smoking history, patients'age and sex (P>0.05). The positive expression rate of CXCR4 protein in metastasis lymph node tissue (76.47%) is higher than those in nonmetastasis lymph node tissue (8.70%), there is statistic significance (P<0.01).2.2 The results detected by FCM: The quantitative expression of CXCR4 protein (FI) in laryngeal carcinoma tissues, para- carcinoma and normal laryngeal mucosa tissues respectively is falling down, there is statistic significance (P<0.01). The quantitative expression of CXCR4 protein in laryngeal carcinoma tissues is obviously higher than those in para-carcinoma (P<0.01) and in normal laryngeal mucosa (P<0.01) tissues respectively. No significant difference was found between the expression of para-carcinoma and normal laryngeal mucosa tissues (P>0.05). Expression of SDF-1 was correlated with lymph node metastasis, clinical stage, and pathological grading of tumor (P<0.01), but that wasn't correlated with patients'clinical classification, tumor size, smoking history, patients'age and sex (P>0.05).3 The expression of HIF-1αprotein 3.1 The results detected by IHC: The expression of HIF-1αin laryngo carcinoma, para-carcinoma, normal laryngeal mucosa tissues and cervical lymph node tissue by S-P immunohistochemical methods. The expression of HIF-1αin laryngocarcinoma, para-carcinoma and normal laryngeal mucosa tissues is falling down, there is statistic significance (P<0.01). The expression of HIF-1αin laryngocarcinoma is obviously higher than those in para-carcinoma (P<0.01) and in normal laryngeal mucosa (P<0.01) tissues respectively. No significant difference was found between the expression of para-carcinoma and normal laryngeal mucosa tissues (P>0.05). Expression of HIF-1αwas correlated with lymph node metastasis (P<0.05), clinical stage (P<0.01) and pathological grading of tumor (P<0.05), but that wasn't correlated with patients'clinical classification, tumor size, smoking history, patients'age and sex(P>0.05). The positive expression rate of HIF-1αprotein in metastasis lymph node tissue (76.47%) is higher than those in nonmetastasis lymph node tissue (3.33%), there is statistic significance (P<0.01).3.2The results detected by FCM: The quantitative expression of HIF-1αprotein (FI) in laryngeal carcinoma tissues, para- carcinoma and normal laryngeal mucosa tissues respectively is falling down, there is statistic significance (P<0.01). The quantitative expression of HIF-1αprotein in laryngeal carcinoma tissues is obviously higher than those in para-carcinoma (P<0.01) and in normal laryngeal mucosa (P<0.01) tissues respectively. No significant difference was found between the expression of para-carcinoma and normal laryngeal mucosa tissues (P>0.05). Expression of HIF-1αwas correlated with lymph node metastasis (P<0.01), clinical stage (P<0.05) and pathological grading of tumor (P<0.01), but that wasn't correlated with patients'clinical classification, tumor size, smoking history, patients'age and sex (P>0.05).4 There is multiple linear regression relationship in the expression of SDF-1, CXCR4 and HIF-1αIn laryngeal carcinoma, and it is a positive correlation. The expression of SDF-1 and CXCR4 increase along with that of HIF-1αincreases. The multiple linear regression equation is YH=0.630+0.283XS+0.404XC (F=6.708,P =0.003) .Conclusions:1 The three indexes, SDF-1, CXCR4 and HIF-1α, express in all laryngeal carcinoma, para-carcinoma mucosa and normal mucosa tissues.2 The quantitative and qualitative expression of the SDF-1, CXCR4 and HIF-1αin laryngeal carcinoma tissues are obviously higher than those in para-carcinoma and normal laryngeal mucosa tissues, which could probably prove the relationship between the the indexes and laryngeal carcinoma.3 The expression of SDF-1, CXCR4 and HIF-1αprotein are correlated with malignant biological behavior of laryngeal squamous cell carcinoma, which included lymph node metastasise, clinical stage and pathological grading of the tumor. But they aren't related to patients'clinical classification, tumor size, smoking history, patients'age and sex. The co-operation of SDF-1, CXCR4 and HIF-1αprotein may play cooperation role in lymphatic metastasis of laryngeal carcinoma.4 The three indexes, SDF-1, CXCR4 andHIF-1α, express in metastasis lymph node tissue is obviously high than express in nonmetastasis lymph node tissue.5 There is an direct correlation between the quantitative expression of SDF-1, CXCR4 and HIF-1αprotein, the expression of SDF-1 and CXCR4 increase along with that of HIF-1αincreases.
Keywords/Search Tags:Laryngeal carcinoma, chemokines, SDF-1, CXCR4, HIF-1α, lymphatic-metastasis, immunohistochemistry (IHC), flow cytometry (FCM)
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