GDNF及其受体在腺样囊性癌中的表达及意义
摘要
目的:
研究胶质细胞源性神经营养因子GDNF及其受体在涎腺腺样囊性癌(salivary adenoid cystic carcinoma SACC)中的表达特点,探讨其表达与腺样囊性癌临床病理特征及嗜神经侵犯的关系。
材料与方法:
1.选取SACC36例,粘液表皮癌(mucoepidermoid carcinoma MEC)15例,正常腮腺组织10例;收集年龄、部位、神经浸润、临床分类、病理分级等资料。
2.采用免疫组织化学SP法检测36例SACC,15例MEC,10例正常腮腺石蜡切片中GDNF及其受体GFRα-1、RET的表达。15例MEC、10例正常腮腺作对比研究。
3.统计分析SACC、MEC和正常腮腺中GDNF及其受体表达的差异;分析GDNF及其受体的表达与SACC各临床病理参数以及与嗜神经侵犯之间的关系。
结果:
1.在正常腮腺的腺泡细胞中未见GDNF、GFRα-1、RET阳性表达,在导管细胞中GDNF50%阳性表达,GFRα-1 40%阳性表达,RET未见阳性表达。
2.在SACC中GDNF的阳性率为88.9%(32/36),GFRα-1的阳性率83.3%(30/36),GDNF和GFRα-1的表达和患者肿瘤部位无显著相关性(P＞0.05);在SACC的各个病理分型中表达无显著差异(P＞0.05);二者在SACC高分期中表达强度高于低分期(P＜0.05);在存在嗜神经现象组,二者的表达明显高于未见嗜神经现象组(P＜0.05)。且7例强阳性表达者,GDNF的表达强度从神经至周围呈减弱趋势。
3.粘液表皮癌中GDNF、RET表达为阴性,GFRα-1有6例表达阳性。
4.GDNF及GFRα-1表达水平的组间对比:腺样囊性癌组明显高于粘液表皮癌组及正常腮腺组(P＜0.05)。
结论:
1、GDNF及其受体在正常腮腺组织及粘液表皮癌中不表达或弱表达,在SACC癌组织表达明显增强,GDNF有可能作为SACC嗜神经侵袭的生物学标志之一。
2、GDNF与其受体的相互作用可能在腺样囊性癌的侵袭转移及嗜神经侵犯中扮演重要角色。
Objective:To study the expression of glial cell line-derived neurotrophic factor(GDNF)and GDNF receptors(GFRα-1、RET)in salivary adenoid cystic carcinoma(SACC)and explore it's relationship with the clini-pathological features and biological behavior of SACC.
Materials and Methods:
1.10 normal parotid gland、36 salivary adenoid cystic carcinoma (SACC)and 15 Mucoepidermoid carcinoma(MEC)were selected. Clinical information was collected including patient age,location, pathological type,perineural invasion and clinical stage et al.
2.Using immuohistochemical SP staining,we examined protein GDNF and it's receptors expression in paraffin slices of 36 salivary adenoid cystic carcinoma.As control,expression of these proteins in 15 MEC and 10 normal parotid gland were also detected.
3.Difference of GDNF and it's receptors were analyzed in normal parotid gland、MEC and SACC.Relationships of these proteins expressiom with clini-pathological parameter were analyzed in SACC.
Rresult:
1、In the gland alveolus cells of normal parotid gland,GDNF and it's receptoe didn't express;In the ductal cells of normal parotid gland,the positive expression rate of GDNF is 50%(5/10),the positive expression rate of GFRα-1 is 40%(4/10).RET didn't find positive expression.
2、In the SACC,the positive expression rates of GDNF is 88.9%(32/36);the positive expression rates of GFRα-1 is 83.3%(30/36); Expression of GDNF and GFRα-1 had no correlation with location, pathological type(P＞0.05),But it had correlation with clinical stage and perineural invasion(P＜0.05),And seven cases of strong positive expression,their GDNF expression had a weakening trend from the nerve to peripheral carcinoma.
3、In the Mucoepidermoid carcinoma,GDNF and RET didn't express;the positive expression rate of GFRα-1 is 40.0%(6/15).
4.The positive expression rates of GDNF and GFRα-1 has statistical significance between the SACC、Mucoepidermoid carcinoma and normal parotid gland.
Conclusions:
1、In the normal parotid gland and Mucoepidermoid carcinoma, GDNF and GFRα-1 didn't exoress or had a poor expression,however,In the SACC,GDNF and GFRα-1 expressed significantly;GDNF and it's receptor may be as one of the biological signs with perineural invasion of SACC.
2.GDNF and GFRα-1 may play an importent role in the infiltration and perineural invasion of SACC.
研究胶质细胞源性神经营养因子GDNF及其受体在涎腺腺样囊性癌(salivary adenoid cystic carcinoma SACC)中的表达特点,探讨其表达与腺样囊性癌临床病理特征及嗜神经侵犯的关系。
材料与方法:
1.选取SACC36例,粘液表皮癌(mucoepidermoid carcinoma MEC)15例,正常腮腺组织10例;收集年龄、部位、神经浸润、临床分类、病理分级等资料。
2.采用免疫组织化学SP法检测36例SACC,15例MEC,10例正常腮腺石蜡切片中GDNF及其受体GFRα-1、RET的表达。15例MEC、10例正常腮腺作对比研究。
3.统计分析SACC、MEC和正常腮腺中GDNF及其受体表达的差异;分析GDNF及其受体的表达与SACC各临床病理参数以及与嗜神经侵犯之间的关系。
结果:
1.在正常腮腺的腺泡细胞中未见GDNF、GFRα-1、RET阳性表达,在导管细胞中GDNF50%阳性表达,GFRα-1 40%阳性表达,RET未见阳性表达。
2.在SACC中GDNF的阳性率为88.9%(32/36),GFRα-1的阳性率83.3%(30/36),GDNF和GFRα-1的表达和患者肿瘤部位无显著相关性(P＞0.05);在SACC的各个病理分型中表达无显著差异(P＞0.05);二者在SACC高分期中表达强度高于低分期(P＜0.05);在存在嗜神经现象组,二者的表达明显高于未见嗜神经现象组(P＜0.05)。且7例强阳性表达者,GDNF的表达强度从神经至周围呈减弱趋势。
3.粘液表皮癌中GDNF、RET表达为阴性,GFRα-1有6例表达阳性。
4.GDNF及GFRα-1表达水平的组间对比:腺样囊性癌组明显高于粘液表皮癌组及正常腮腺组(P＜0.05)。
结论:
1、GDNF及其受体在正常腮腺组织及粘液表皮癌中不表达或弱表达,在SACC癌组织表达明显增强,GDNF有可能作为SACC嗜神经侵袭的生物学标志之一。
2、GDNF与其受体的相互作用可能在腺样囊性癌的侵袭转移及嗜神经侵犯中扮演重要角色。
Objective:To study the expression of glial cell line-derived neurotrophic factor(GDNF)and GDNF receptors(GFRα-1、RET)in salivary adenoid cystic carcinoma(SACC)and explore it's relationship with the clini-pathological features and biological behavior of SACC.
Materials and Methods:
1.10 normal parotid gland、36 salivary adenoid cystic carcinoma (SACC)and 15 Mucoepidermoid carcinoma(MEC)were selected. Clinical information was collected including patient age,location, pathological type,perineural invasion and clinical stage et al.
2.Using immuohistochemical SP staining,we examined protein GDNF and it's receptors expression in paraffin slices of 36 salivary adenoid cystic carcinoma.As control,expression of these proteins in 15 MEC and 10 normal parotid gland were also detected.
3.Difference of GDNF and it's receptors were analyzed in normal parotid gland、MEC and SACC.Relationships of these proteins expressiom with clini-pathological parameter were analyzed in SACC.
Rresult:
1、In the gland alveolus cells of normal parotid gland,GDNF and it's receptoe didn't express;In the ductal cells of normal parotid gland,the positive expression rate of GDNF is 50%(5/10),the positive expression rate of GFRα-1 is 40%(4/10).RET didn't find positive expression.
2、In the SACC,the positive expression rates of GDNF is 88.9%(32/36);the positive expression rates of GFRα-1 is 83.3%(30/36); Expression of GDNF and GFRα-1 had no correlation with location, pathological type(P＞0.05),But it had correlation with clinical stage and perineural invasion(P＜0.05),And seven cases of strong positive expression,their GDNF expression had a weakening trend from the nerve to peripheral carcinoma.
3、In the Mucoepidermoid carcinoma,GDNF and RET didn't express;the positive expression rate of GFRα-1 is 40.0%(6/15).
4.The positive expression rates of GDNF and GFRα-1 has statistical significance between the SACC、Mucoepidermoid carcinoma and normal parotid gland.
Conclusions:
1、In the normal parotid gland and Mucoepidermoid carcinoma, GDNF and GFRα-1 didn't exoress or had a poor expression,however,In the SACC,GDNF and GFRα-1 expressed significantly;GDNF and it's receptor may be as one of the biological signs with perineural invasion of SACC.
2.GDNF and GFRα-1 may play an importent role in the infiltration and perineural invasion of SACC.
引文
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[2]Fanburg-smith JG,Miettinen M.Low-affinity nerve growth factor receptor(p75)in dermatofibrosarcoma protuberans and other nonneural tumaors:a study of 1,150 tumors and fetal and adult normal tissues[J].Hum Pathol,2001,32(9):976-983.
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[4]NagakawaO,MurakamiK,YamauraT,etal.Expressionofmembrane-type 1 matrix metalloproteinase(MT1-MMP)onprostatecancercelllines.Cancer-Lett,2000,155(2):173-179
[5]Labouyrie E,Dubus P,Groppi A,et al.Expression of neuotrophins and their receptors in human bone marrow[J].American journal of pathology,1999,15(2):405-415
[6]Miknyoczki SJ,Wan W,Chang H,et al.The neurotrophin-trk receptor axes are critical for the growth and progression of human prostatic carcinoma and pancreatic ductal adenocarcinoma xenografts in nude mice[J]Clinical cancer Research,2002,8(6):1924-1931
[7]Ricci A,Greco S,Mariotta S,et al.NT and NT receptors in human lung cancer[J].Am J Respir Cell Mol Biol,2001,25(4):439-446
[8]陈伟,孙沫逸,王磊等.酪氨酸激酶B在唾液腺腺样囊性癌中的表达及与嗜神经侵袭的关系[J].现代肿瘤医学,2004,12(5):388-390
[9]Guado F,Majo G,et al.Trk neurotrophin receptor amily immunoreactivity in rat and human pituitary tissues[J].Neurosci Lett,1998,243(1):13-16
[10]Sclabas GM,Fujioka S,Schmidt C,et al.Overexpression of tropomysin-related kinase B in metastatic human pancreatic cancer cells[J].Clinical Cancer Res,2005,11(2):440-449
[11]Nakagawara A,Trk receptor tyrosine kinases:abridge between cancer and neural development[J].Cancer Lett,2001,169(2):107-114
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