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食管鳞癌组织中c-fos,c-jun及PCNA的表达及临床病理意义

Biopatholgical Significance of the Abnomal Expression of c-fos, c-jun and PCNA in Esophageal Cancer Tissues

【作者】 罗庆元

【导师】 蒋莹;

【作者基本信息】 新疆医科大学 , 内科学, 2009, 硕士

【摘要】 目的:食管癌是我国最常见的恶性肿瘤之一,在我国食管癌的死亡率居恶性肿瘤的第四位,通过长期细胞学、内窥镜活检及手术切除标本等资料研究证实,人食管粘膜上皮的癌变是一个长期的、多阶段与进行性发展的过程。食管癌的癌变机制与细胞的增殖、分化、凋亡调控失常密切相关,多种癌基因及肿瘤抑制基因参与了其发生发展的过程。有促进作用。目前,原癌基因的生理功能愈来愈引起重视,c-fos和c-jun是编码核蛋白的癌基因,属于立早基因的成员,此类基因受到多种刺激后立即表达,产生转录因子,调控其他基因的转录及表达,调节正常细胞的生长、发育和分化,并且与肿瘤分级、临床分期及浸润转移有关。国内外的研究亦表明PCNA已成为恶性肿瘤增殖期细胞的有效标志物,在肝、胃、乳腺和大肠等肿瘤研究中发现,PCNA的表达与肿瘤分级、临床分期及浸润转移有关。本研究检测原癌基因c-fos, c-jun和PCNA在原发性食管鳞状细胞癌的表达情况,探讨其临床病理学意义及两者与食管鳞状细胞癌的发生发展的关系。方法:选取2004年1月-2007年1月于新疆医科大学附属第二附属医院病理科经手术切除及活检存档的蜡块,其中采用免疫组化染色SP法,检测60例食管鳞状细胞癌、20例重度上皮内瘤变和10例正常食管粘膜组织标本中c-fos,c-jun和PCNA的表达。结果:(1)60例食管癌组织,20例重度上皮内瘤变和10例正常食管粘膜组织标本中c-fos的阳性表达率分别为56%(51/60),75%(15/20)和0,差异有统计学意义(P<0.05),c-jun的阳性表达率分别为38%(23/60),55%(11/20)和10%(1/10),差异有统计学意义(P<0.05),而PCNA的阳性表达率分别为70%(42/60),50%(10/20)和10%(1/10),差异有统计学意义(P<0.05)。(2)c-fos和c-jun在高分化食管癌中的表达率显著高于中、低分化癌(P<0.01);无淋巴结转移者表达率高于有淋巴结转移者,临床分期Ⅰ-Ⅱ表达率高于Ⅲ-Ⅳ期(P<0.05)。而PCNA的表达相反。(3)在食管鳞状细胞癌中,c-fos与c-jun的蛋白表达情况的Spearman等级相关系数为0.399,具有统计学差异(P<0.05)。(4)c-fos, c-jun和PCNA术前活检组织和术后病理组织表达无统计学差异(P>0.05)。结论:c-fos, c-jun和PCNA的过表达可能均参与了食管鳞状细胞癌的发生发展过程,并可能作为监测肿瘤恶性程度和诊断的指标。

【Abstract】 Objective:Esophageal carcinoma is a kind of common maglignant tumor in china.It was the fourth in the death rate of malignant tumor in our country.Themost.The research has shown tha the carcerrization of epidermis of mueous membrane of People’s esophagus is along-temr, multistage and progressing process of development. the cancerization mechanism of esophageal carcinoma is closely related to the proliferation, differentiation and disorder of decease and regulation & control of cells.Many kinds of cancer genes and tumor cheeking genes take part in the occurrence & development of it. The hysiology function of proto oncogene causing various,incitement and more c-fos and c-jun are the cancer genes which code to check nuclear protein.belong to the early gene this kind of gens is subjected to immediately express by various incitement and produce to transcript factor.This kind of gene adjust to contro ltranseription and expresstion of other geneses and regulate the growth, development and division of normal cell. And have shown that the expressions of c-fos and c-jun are related to the classification of tumrors, clinical stages and the soakage & metasastis.The research of both home and abroad has also shown thatpoliferating cell nuclear natigen(PCNA) is an effectiven symbol of the malingantTumor cells in the period of proliferation.The studies of livesr, stomach, galactophore and intestinum crassmu have shown that the expressions of PCNA are related to the classification of tumrors, clinical stages and the soakage & metasastis.To investigate the expression of c-fos,c-jun and PCNA inprimar esophageal squamous cellcarcinoma and to evaluate whether these Alterations could provide clinical significant informations. Methods:Select wax lumps were cutted off by 2004 at the xinjiang medieinedepartment University the second affiliated Hospital,The expression of c-fos, c-jun and PCNA was studied by StrePtavidin Peroxidase(SP) immunohisto chemical methodwas used to detect the expressions of c-fos,c-jun and PCNA and to analyse the correlation between them and different clinical pathological features in 60 cases of esophageal squamous cell carcinoma, in 20 cases of abnormal and in 10 cases of normal esophageal tissues.Results:(1) The positive frequency of c-fos in 60 cases of esophageal squamous cell carcinoma, in 20 cases of abnormal and in 10 cases of normal esophageal tissues was respectively 56%(51/60),75%(15/20)and 0, The group had significant difference (P<0.05). The positive frequency of c-jun was respectively 38%(23/60),55 %(11/20)和10%(1/10),The group had significant difference (P<0.05).But the positive frequency of PCNA was respectively 70%(42/60),50%(10/20) and 10%(1/10) The group had significant difference (P<0.05).(2) The positive ratio of c-fos, c-jun and PCNA proteinwas significantly higher in thewell differentiated and moderately differentiated esophageal carcinomas than in the poorly differentiated esophageal carcinomas(P<0.05). The esophageal carcinomas with lymph node metastasis expressed c-fos, c-jun and PCNA protein more markedly than those without lymphnode metastasis(P<0.05). (3) In carcinoma samples, the expression of c-fos protein was Positively correlated with that of c-jun(spearman rho 0.399, P<0.05). (4) the expression of c-fos,c-jun and PCNA at the preoperative biopsy and afteroperative pathology tissue were no significant relationship with either clinical stage (P>0.05).Conclusions:The overexpression of c-fos, c-jun and PCNA could serve as an important index in the aspect of invasiveness and metastasis in esophageal squamous cell carcinoma,and might be used as valuable molecular markers for the tumor progression and diagnose.

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