△Np63、p21^(WAF1)及MDM2基因蛋白在鼻咽癌组织表达的研究

The expression of △Np63,p21^(WAF1) and MDM2 protein in nasopharyngeal carcinoma and their significance

目的 :探讨鼻咽癌组织中△Np6 3、p2 1WAF1 和MDM2蛋白的表达及意义。方法 :采用免疫组化方法研究△Np6 3、p2 1WAF1 和MDM2蛋白在 6 0例鼻咽癌活检组织的表达 ,6 0例鼻咽癌的组织类型包括角化性鳞癌 3例 ;非角化性癌 5 7例 ,其中含未分化癌 12例。结果 :6 0例鼻咽癌抗△Np6 3染色成不同程度阳性反应 ,表现为细胞核棕黄色。其中角化性鳞癌呈弱阳性表达 ,癌巢周边基底样细胞阳性略呈环状分布 ,或弥散分布 ;非角化性癌多呈强阳性反应 ,染色深 ,呈弥漫或片状分布 ,癌旁粘膜及正常鼻咽粘膜仅基底层和上基层细胞呈阳性表达。p2 1WAF1 在鼻咽癌、癌旁上皮及正常粘膜上皮的阳性率分别为 2 6 %、15 %、7% ,在三组的表达无显著性差异 ;MDM2在鼻咽癌、癌旁上皮及正常粘膜上皮的阳性率分别为 19%、5 %、4 % ,在癌组和非癌组表达有显著性差异。结论 :△Np6 3蛋白在鼻咽非角化性癌中高表达 ,表明与细胞恶性增生密切相关 ,可能在癌细胞多相性退分化中起作用 ,是鼻咽非角化性癌有价值的诊断指标。MDM2在鼻咽癌组的表达显著高于对照组 ,起癌基因作用。△Np6 3和MDM2均抑制p5 3转录活性 ,使NPC中p5 3虽然无突变却缺乏失活。p5 3活性低则不能上调p2 1WAF1 ,G1 关卡失去功能 ,形同虚设。△Np6 3及MDM2高表达和p2 1WAF1

Objective:To study the expression and significance of △Np63,p21 WBF1 and MDM2 protien in nasopharyngeal carcinoma(NPC).Methods:△Np63,p21 WAF1 and MDM2 antibody was used for immunocytochemical stain to study 60 NPC tissue samples(3 cases of keratin squamous cell carcinoma and 57 cases of non keratin cell carcinoma including 12 cases of undifferentiated carcinoma).Results:All together 60 cases were positive for △Np63 immunocytochemical stain in varying degrees showing cell nuclear in brown.Keratin squamous cell carcinoma was lightly stained and positive basal like cells of nests range somewhat in a ring,sometimes with a few scatter distribution.However,there were heavily stained in the non keratinizing cell carcinoma,all contain large number of nuclei in deep stain and scatter distribution.The nearby mucosa and normal nasopharyngeal mucosa showed basal and superbasal layer possitive stain only.The distribution of positive rate of p21 WAF1 protien in tumor tissues and nearby mucosas and normal nasopharyngeal tissues were 26%,15%,7% respectively,there are no significant difference.The distribution of positive rate of MDM2 protien in tumor tissues and nearby mucosas and normal nasopharyngeal tissues were 19%,5%,4% respectively,there are significant difference.Conclusion:It is high level expression of △Np63 protein in non keratin carcinoma.It represent its effect on malignancy hyperplasia and play a role in the cells polyphasic anaplasia,△Np63 antibody is a valuable diagnostic marker for non keratin carcinoma in nasopharynx.The MDM2 expression is still significantly higher than control group,it acts as oncogene in NPC.Both △Np63 and MDM2 suppress the transcriptional activity of p53 gene that result in p53 no mutation but inactivation in NPC.Consequently,inactivated p53 can not increase the expression of p21 WAF1 making a malfunction in G 1 check point of the cells cycle.These results indicate that high expression of △Np63 and MDM2 joint a low expression of p21 WAF1 abrogate the tumor suppress or function of p53 and causing NPC escapes from p53 control.