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The Expressions of GEFR, VEGFR1/Flt-1, MGMT and TopoIIa in Esophageal Squamous Cell Carcinoma Tissues with Or Without Radiotherapy

Author: LiQiFeng
Tutor: WuMingYao
School: Shantou University
Course: Pathology and Pathophysiology
Keywords: esophageal neoplasm radiotherapy EGFR VEGFR1/Flt-1 MGMT Topoisomerasell alpha
CLC: R735.1
Type: Master's thesis
Year: 2011
Downloads: 23
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Abstract


Background and objectiveEsophageal cancer is one of most common malignant tumor in the world, themortality rate on the top 10 in malignant tumor. Shantou area of eastern Guangdongprovince has a very high morbidity and mortality of esophageal cancer. For a long time,esophagectomy is the most effective treatment method for esophageal cancer, whoevercan excision of esophagus cancer, surgery is the preferred treatment. But most patientshave already lost the chance of surgery in the middle-late period, with the 5-year survivalrate less than 10%[1]. Now extensive think that surgical combined with radiotherapy andchemotherapy is a comparatively mature therapy for esophageal cancer. Radiotherapycan make cancer cells degenerate, losing activity, reduce the volume of tumor, vascularthrombosis and eliminate small metastases. Preoperative radiotherapy of esophagealsquamous cell carcinoma can improve the resection rate, reduce postoperativeinstallment, improving local control rate. This study aims to explore the radiotherapysensitive indicators of esophageal cancer, analysis the radiotherapy sensitive indicators’significance and application value on the individual therapy of esophageal cancer.MaterialsThe samples were collected from the department of pathology of Shantou universitymedical college, including surgically resected tumor specimens of esophagealsquamous cell carcinoma (40 cases) between 2007-2008, and 40 cases of preoperativeradiotherapy of esophageal cancer resected specimens between 1996-2008, as well asadjacent normal esophageal tissues (20 cases) were collected.Methods1.HE stain: Cell morphology was observed by light microscope after HE stain and allcases were made histological diagnosis for futher histological classification.2.Immunohistochemistry:The Envision Labelled Peroxidase System (ELPS) was usedto detected the expression of EGFR protein, VEGFR1/Flt-1 protein, MGMT protein,Topoisomerase II alpha protein in the paraffin sections by immunohistochemistry. 3.The sections were taken five images randomly using Leica DMRXA2Almightymicroscope and Leica IM50 image acquisition system. According to the results of eachsection dyeing rating and analysis.StatisticaStatistical analysisStatistical analysis were performed using Descriptive Statistics and BivariateCorrelations. A P-value of less than 0.05 was considered to be significant.Results1.Morphologic changes after radiotherapy in esophageal cancertissues[2]Most esophageal specimens had mild mucosal hyperplasia with submucosalinflammatory changes and some cancer cells remained after radiotherapy ofesophageal cancer. The most obvious histological change was general degeneration oftumor cells in different degrees (grade I radiotherapy response) and formation thegranuloma (grade II radiotherapy response). Remaining degenerative cancer cells wereall vacuolar, swollen or condensed in HE staining. Slight to moderate degree infiltrationof inflammatory cells around the degenerative cancer cells were observed. Accordingto the HE stain, there are 14 cases of grade I radiotherapy response, 26 cases of gradeII radiotherapy response.2.The expression of EGFR protein in esophageal tissueThere is no EGFR expression in normal esophageal tissues, but for the expression ofEGFR in esophageal squamous cell carcinoma without radiotherapy rising obviously to77.5%. Compared with the normal esophageal tissue with explicit statistical significance(P<0.01). The expression of EGFR in esophageal squamous cell carcinoma withradiotherapy declined to 62.5%. Compared with the esophageal squamous cellcarcinoma without radiotherapy with statistical significance (P=0.007,P<0.05). Theexpression of EGFR has no statistical significance between esophageal squamous cellcarcinoma without radiotherapy and esophageal squamous cell carcinoma withradiotherapy for the histological grade, invasion deepth, and lymph node metastasis (P>0.05). The grade I radiotherapy response compared with grade II radiotherapyresponse has no statistical significance (P>0.05).3.The expression of VEGFR1/Flt-1 protein in esophageal tissueWe observed 80% VEGFR-1/Flt expression in normal esophageal tissues, but declinedin esophageal squamous cell carcinoma without radiotherapy to 62.5%, Compared withthe normal esophageal tissue has no significance (P=0.078,P>0.05). The expression ofVEGFR-1/Flt in esophageal squamous cell carcinoma with radiotherapy rised to 80%,Compared with the esophageal squamous cell carcinoma without radiotherapy withstatistical significance (P=0.035,P<0.05). The expression of VEGFR-1/Flt has nostatistical significance in esophageal squamous cell carcinoma without radiotherapy andesophageal squamous cell carcinoma with radiotherapy for the histological grade,invasion deepth, and lymph node metastasis (P>0.05). The grade I radiotherapyresponse compared with grade II radiotherapy response has no statistical significance(P>0.05).4.The expression of MGMT protein in esophageal tissueThere is 100% MGMT expression in normal esophageal tissues, declined to 50% inesophageal squalors cell carcinoma without radiotherapy, Compared with the normalesophageal tissue with explicit statistical significance (P<0.01). The expression ofMGMT was rised to 72.5% with radiotherapy in esophageal squamous cell carcinoma.Compared with the esophageal squamous cell carcinoma without radiotherapy withstatistical significance (P=0.004,P<0.05). The expression of VEGFR-1/Flt has nostatistical significance in esophageal squamous cell carcinoma without radiotherapy forthe histological grade, invasion depth, and lymph node metastasis (P>0.05), Theexpression of MGMT has no statistical significance in esophageal squamous cellcarcinoma with radiotherapy for invasion depth, but has statistical significance for thehistological grade, and lymph node metastasis (P=0.033 and P=0.026,P<0.05). Thegrade I radiotherapy response compared with grade II radiotherapy response has nostatistical significance (P>0.05). 5.The expression of Topoisomerase II alpha protein in esophagealtissutissueHere is 35% Topo-IIa expression in normal esophageal tissues, rised to 80% inesophageal squamous cell carcinoma without radiotherapy, Compared with the normalesophageal tissue with explicit statistical significance (P<0.01). The expression ofTopo-IIa was rised to 20% with radiotherapy in esophageal squamous cell carcinoma.Compared with the esophageal squamous cell carcinoma without radiotherapy withexplicit statistical significance (P<0.01). The expression of Topo-IIa has no statisticalsignificance in esophageal squamous cell carcinoma without radiotherapy andesophageal squamous cell carcinoma with radiotherapy for the histological grade,invasion depth, and lymph node metastasis (P>0.05). The grade I radiotherapy responsecompared with grade II radiotherapy response has no statistical significance (P>0.05).Conclusion1.It was a statistical significance about the expressions of EGFR、MGMT andTopoisomerase II alpha protein in esophageal squamous cell carcinoma withoutradiotherapy and normal esophageal tissue. Therefore, EGFR, VEGFR1/Flt-1, MGMTand Topoisomerase II alpha plays an important role in the process of esophagealcarcinogenesis.2.The expressions of EGFR, VEGFR1/Flt-1, MGMT and Topoisomerase II alpha proteinin esophageal squamous cell carcinoma with or without radiotherapy have a statisticalsignificance. It suggested that EGFR, VEGFR1/Flt-1, MGMT and Topoisomerase II alphawere probably as an independent indicator to predict the sensitivity of radiotherapy inpatients with esophageal squamous cell carcinoma.3. There is no correlation between the expession of EGFR and VEGFR1/Flt-1 inesophageal squamous cell carcinoma with or without radiotherapy. It prompt that thesetwo proteins play an alone role in the process of carcinogenesis, infiltration, transfer andprognosis in esophageal squamous cell carcinoma.4.The expression of MGMT and Topoisomerase II alpha has a positive correlation inesophageal squamous cell carcinoma with radiotherapy, but has a negative. It promptthat these two proteins play an antagonism role in the process of carcinogenesis,infiltration, transfer and prognosis in esophageal squamous cell carcinoma.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Esophageal tumors
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