【作者】 茹艺；

【导师】 冯笑山；

【作者基本信息】 河南科技大学 ， 肿瘤学， 2011， 硕士

【摘要】 目的探讨p57^kip2蛋白、cyclinD1蛋白在贲门癌组织及贲门各级病变组织中的表达与贲门癌发生发展的关系及临床意义。方法收集河南科技大学第一附属医院胃镜活检贲门组织以及贲门癌手术标本共计130例。分为4组:贲门炎组织24例、贲门不典型增生组织26例、贲门癌组织60例及对照组正常贲门黏膜组织20例。采用免疫组织化学SP法,分别检测各组组织中p57^kip2、cyclinD 1蛋白的表达情况;利用SPSS软件分析各组间p57^kip2、cyclinD1蛋白表达的差异。分析其与贲门癌之间的相关性。并将免疫组化结果与临床病理参数进行比较分析。结果p57^kip2蛋白在贲门粘膜各病变组织中的表达分别为:在贲门炎组中阳性表达率87.5% （21/24）,显著高于贲门不典型增生组53.8% （14/26） （P<0.05）,不典型增生组与贲门癌组43.4% （26/60）之间无显著性差异（P>0.05）,随着病变进展,其阳性表达率逐渐降低。经统计学分析p57^kip2蛋白表达在各组间的表达差异具有统计学意义。p57^kip2蛋白在正常贲门上皮组织中的表达水平为90% （18/20）,p57^kip2蛋白在贲门癌组织中的表达水平为43.4% （26/60）,两者差异具有显著性（P<0.05）。p57^kip2蛋白在Ⅰ期贲门癌中的表达率是71.4% （10/14）,在Ⅱ期贲门癌组织中的表达率是41.4% （12/29）,在Ⅲ期贲门癌组织中的表达率是23.5% （4/17）,该结果有统计学意义（P<0.05）。p57^kip2蛋白在高、中分化贲门癌组织中的表达率分别是66.7% （8/12）、57.1% （12/21）,显著高于其在低分化贲门癌组织中的表达率22.2% （6/27）,该结果有统计学意义（P<0.05）;有淋巴结转移组患者p57^kip2蛋白阳性表达率为44.1% （15/34）,无淋巴结转移组患者p57^kip2蛋白阳性表达率为42.3% （11/26）,两者差异不具有显著性。cyclinD1蛋白在贲门粘膜各病变组织中的表达分别为:cyclinD1蛋白在贲门癌组中阳性表达率53.3% （32/60）,显著高于不典型增生组30.8% （8/26） （P<0.05）,不典型增生组与贲门炎组29.2% （7/24）之间无显著性差异（P>0.05）,随着病变进展,其阳性表达率逐渐升高。经统计学分析cyclinD1蛋白表达在各组间的表达差异具有统计学意义。cyclinD1蛋白在正常贲门上皮组织中的表达水平为25% （5/20）,其在贲门癌组织中的表达水平为53.3% （32/60）,两者相比差异具有统计学意义（P<0.05）。cyclinD1蛋白在Ⅰ期贲门癌中的表达率是28.6% （4/14）,在Ⅱ期贲门癌组织中的表达率是51.7% （15/29）,在Ⅲ期贲门癌组织中的表达率是76.5% （13/17）,该结果有统计学意义（P<0.05）。cyclinD1蛋白在高、中、低分化贲门癌组织中的表达率分别是58.3% （7/12）、52.4% （11/21）和51.9% （14/27）,该结果不具有统计学意义;有淋巴结转移组患者cyclinD1蛋白阳性表达率为70.6% （24/34）,无淋巴结转移组患者cyclinD1蛋白阳性表达率为30.8%（8/26）,两者差异具有显著性（P<0.05）。p57^kip2与cyclinD1表达的相关性:p57^kip2阳性表达的26例贲门癌中,cyclinD1阳性表达者5例（19.2%）,在p57^kip2阴性表达的34例贲门癌中,cyclinD1阳性表达者29例（85.3%）,提示p57^kip2和cyclinD1在贲门癌组织中的表达呈负相关（r=-0.661, P<0.01）。结论1、p57^kip2蛋白在贲门炎、不典型增生组织及癌变组织中的表达差异具有统计学意义,并与贲门癌分期和分化程度相关。提示p57^kip2基因表达缺失与贲门癌发生、发展有关。p57^kip2蛋白表达的水平可以作为判定贲门癌恶性程度高低的标记,对临床的诊断具有一定的指导意义。2、cyclinD1蛋白在贲门炎、不典型增生组织及癌变组织中的表达差异具有统计学意义,并与贲门癌分期和有无淋巴结转移相关。提示:对cyclinD1蛋白的检测可能对于贲门癌前病变及早期贲门癌的诊断有参考价值并且在贲门癌的恶性演进过程中可能发挥重要作用。3、p57^kip2、cyclinD1均为重要的细胞周期调控基因,p57^kip2失表达与cyclinD1高表达在贲门癌的发生上可能具有协同作用,联合检测p57^kip2与cyclinD1蛋白可能为临床检测和诊断贲门癌提供更多的生物学信息。更多还原

【Abstract】 Objective Clinical significance and relation of the p57^kip2、cyclinD1 expression in gastric cardia cancer and different grade lesions of gastric cardia tissue.Methods One hundred and thirty case of gastroscope biopsies and surgical specimens of gastric cardia were collected at The first affiliated hospital of Henan university of science and technology. All specimens was divided into 4 groups: gastric cardia hilitis 24 case; gastric cardiac atypical hyperplasia 26 case;gastric cardia cancer 60 case and The control group: normal gastic cardia mucosa 20 case.The expression of p57^kip2,cyclinD1 were detected in every group by immunohistochemical S-P methods; The difference of the expression of p57^kip2,cyclinD1 were analyzed during every group by SPSS. Analyzed the correlation between gastric cardia cancer. The results of immunohistochemistry and clinicopathological parameters were analyzed.Result The expression of p57^kip2 in different gastric cardia tissue:the positive expression rate in gastric cardia hilitis group 87.5% （21/24） is significant higher than gastric cardia atypical hyperplasia group 53.8% （14/26） （P<0.05）,there is no significant difference between gastric cardia atypical hyperplasia group and gastric cardia cancer group 43.4% （26/60） （P>0.05） ,with the advancing of disease,the positive expression rate decreased gradually. By the statistic analyzed,the expression of p57^kip2 were different among 4 groups.The expression rate of p57^kip2 in normal mucosa is 90% （18/20）,and in gastric cardia cancer tissue is 43.4% （26/60）,the different between them were obviously.The expression of p57^kip2 protin rate is 71.4% （10/14） in stage I gastric cardia cancer,41.4% （12/29） in stage II and 23.5% （4/17） in stage III,There are statistic significant in this results （P<0.05）.The expression of p57^kip2 in well differerntiated and moderately differentiated 66.7% （8/12）,57.1% （12/21） were significantly higher than poorly diffierentiated 22.2% （4/17） （P<0.05）. The positive expression of p57^kip2in the group with lymph node metastasis is 44.1% （15/34） and not significant different than the group without lymph node metastasis 42.3% （11/26）. The expression of cyclinD1 in different gastric cardia tissue:the positive expression rate in gastric cardia cancer group 53.3% （32/60） is significant higher than gastric cardiac atypical hyperplasia group 30.8% （8/26） （P<0.05）,there is no significant difference between gastric cardia atypical hyperplasia group and gastric cardia hilitis group 29.2% （7/24） （P>0.05） ,with advancing of disease,the positive expression rate increased gradually. By the statistic analyzed,the expression of cyclinD1 is different among 4 groups. The expression rate of cyclinD1 in normal mucosa is 25% （5/20）,and in gastric cardia cancer is 53.3% （32/60）,the differences between them are obviously.The expression of cyclinD1 protin rate is 28.6% （4/14） in stage I gastric cardia cancer, 51.7% （15/29） in stage II and 76.5% （13/17） in stage III, There are statistic significant in this results （P<0.05）.The expression of cyclinD1 in well differerntiated , moderately differentiated and poorly diffierentiated is 58.3% （7/12）、52.4% （11/21） and 51.9% （14/27） respectively,there is no statistical sense among the three groups.The positive expression of cyclinD1 in the group with lymph node metastasis is 70.6% （24/34） and it is significant higher than the group without lymph node metastasis 30.8% （8/26）. The relation between p57^kip2 and cyclinD1:There is 5 specimens expressed cyclinD1 （19.2%） in the 26 p57^kip2 positive gastric cardia cancer specimens,and 29 specimens expressed cyclinD1 （85.3%） in 34 p57^kip2 negative gastric cardia cancer specimens,suggest that p57^kip2 and cyclinD1 has negative correlation in gastric cardia cancer tissue （r=-0.661,P<0.01）.Conclusion 1.The difference of the expression of p57^kip2 protin in gastric cardia hilitis; gastric cardiac atypical hyperplasia and gastric cardia cancer has statistic sense,and correlate wih gastric cardia cancer stages and differentiation grade.Suggest that loss of p57^kip2 gene expression has relation with the occurrence and progression of gastric cardia cancer.The expression level of p57^kip2 protin maybe a mark to determine the malignancy grade of gastric cardia cancer,and may guide the clinical diagnose. 2. The difference of the expression of cyclinD1 protin in gastric cardia hilitis; gastric cardiac atypical hyperplasia and gastric cardia cancer has statistical sense,and correlate wih gastric cardia cancer stages with or without lymph node metastasis.Suggest that the detection of cyclinD1 may helpful to the diagnose of gastric cardia precancerous lesion and earlier gastric cardia cancer and this protin may an important role in the progression in gastric cardia cancer. 3.Both p57^kip2 and cyclinD1 are importment cell cycle control genes, Loss of p57^kip2 expression and high cyclinD1 expression may have synergistic action in the occurrence of gastric cardia cancer, joint detection about p57^kip2 and cyclinD1 may provided more biological information for the clinical detection and diagnosis of gastric cardia cancer.更多还原