Cyclin D1在胃癌中的表达扩增及其生物学意义

目的：研究Cyclin D1蛋白的表达和基因的扩增及其与胃癌发生发展的关系。方法：采用免疫组化和差异聚合酶链反应（DPCR）技术对45例胃癌进行Cyclin D1检测。结果：Cyclin D1蛋白在胃癌中的表达率为57．8％（26／45），高于正常胃组织的20％（9／45），且与胃癌的分化和转移密切相关。胃癌组织Cyclin D1基因扩增的阳性率为48．9％（22／45）。DPCR和免疫组化结果基本一致。结论：Cyclin D1基因在胃癌的发生发展中起重要作用。Cyclin D1的表达和扩增与胃癌细胞的高增殖活性密切相关。     

P16及CyclinD1在胃癌癌变过程中的作用及意义

目的通过检测慢性萎缩性胃炎、胃不典型增生组织及胃癌组织中P16及Cyclin D1蛋白的表达,探讨P16及Cyclin D1与胃癌发生及发展的关系。方法利用免疫组织化学方法检测慢性萎缩性胃炎、胃不典型增生组织及胃癌中P16及Cyclin D1蛋白的表达水平,利用SPSS软件进行胃癌组织中P16及Cyclin D1蛋白表达相关性分析。结果 P16蛋白在慢性萎缩性胃炎组织中的阳性表达率(91.7%)显著高于不典型增生组织(69.2%)及胃癌组织(45%)中的表达(P0.05)。Cyclin D1蛋白在胃癌组织中的阳性表达率(65%)显著高于胃不典型增生组织(34.6%)及慢性萎缩性胃炎组织(29.2%)中的表达(P0.05)。统计学结果显示,胃癌组织中P16及Cyclin D1蛋白的阳性表达率呈显著负相关(P0.05)。结论P16及Cyclin D1蛋白异常表达在胃癌癌变早期即已发生,联合检测P16及Cyclin D1可为胃癌早期诊断提供客观指标。     

口腔鳞癌组织中Cyclin D1、Ki-67基因的表达及意义

目的探讨口腔鳞癌组织中Cyclin D1、Ki-67基因蛋白表达与口腔鳞癌发生、发展的关系。方法取68份口腔鳞癌组织，用免疫组化法检测癌组织中Cyclin D1、Ki-67基因蛋白的表达，用积分PCR方法检测Cyclin D1的基因扩增。结果口腔鳞癌组织中Cyclin D1基因蛋白表达阳性36例(52．9％)，Ki-67基因蛋白表达阳性48例(70．5％)，Cyclin D1与Ki-67基因蛋白表达呈正相关(r=0．7861)，33份(48．5％)口腔鳞癌组织中Cyclin D1基因存在扩增，Cyclin D1基因扩增与Cyclin D1基因蛋白表达无相关性。Cyclin D1基因蛋白的表达与淋巴结转移有关，Ki-67基因蛋白的表达与肿瘤分化程度有关。结论Cyclin D1基因扩增及Ki-67基因蛋白表达水平可作为判断口腔鳞癌预后及其恶性程度的指标。     

E-cadherin,β-catenin,Cyclin D1在胃腺癌中的表达及临床意义

目的:研究E-cadherin,β-catenin,Cyclin D1在胃腺癌组织中的表达,探讨三者的表达及临床病理意义.方法:采用免疫组织化学SP法检测73例胃腺癌组织及18例正常胃黏膜组织中E-cadherin,β-catenin,Cyclin D1蛋白的表达.结果:正常胃黏膜组织中E-cadherin和β-catenin均呈清晰的棕褐色染色在上皮细胞细胞膜.E-cadherin和β-catenin在胃癌细胞中出现细胞质和/或细胞核异常染色,其异常表达率分别为63.01%(46/73)和56.16%(41/73),且两者的异常表达与胃腺癌的分化程度、TNM分期、浸润深度及淋巴结转移相关,与患者的性别、年龄、肿瘤大小无关.胃腺癌中E-cadherin和β-catenin表达密切相关.Cyclin D1在胃腺癌组织中的阳性表达率为67.12%(49/73),明显高于其在正常胃黏膜组织中的表达(0%,0/18),且与胃腺癌的分化程度和淋巴结转移相关.E-cadherin和β-catenin在胃癌中的异常表达与Cyclin D1的过表达呈显著的正相关(r=0.249,r=0.376,P＜0.05).结论:胃腺癌中存在E-cadherin和β-catenin基因的失活及蛋白表达下调.E-cadherin和β-catenin的异常表达可能通过促使或激活Cyclin D1的过表达而参与胃癌的发生和发展.     

LOXL2在胃癌组织中表达及其与PCNA、CyclinD1、MMP-2、MMP-9的关系

目的观察在胃癌组织中赖氨酰氧化酶(LOXL)2的表达变化,探讨其与增殖细胞核抗原(PCNA)、细胞周期素(Cyclin)D1、基质金属蛋白酶(MMP)-2、MMP-9及预后的关系。方法应用免疫组化法检测100例胃癌组织及相应癌旁正常胃组织中的LOXL2、PCNA、Cyclin D1、MMP-2、MMP-9蛋白表达,分析其在胃癌组织中表达与LOXL2的相关性。结果胃癌组织与癌旁正常胃组织相比,LOXL2、PCNA、Cyclin D1、MMP-2、MMP-9蛋白的水平明显增高(P0.05);在胃癌组织中LOXL2、PCNA、Cyclin D1、MMP-2、MMP-9蛋白阳性表达与肿瘤侵犯深度、淋巴结转移、TNM分期密切相关(P0.05),而与肿瘤大小、肿瘤分化程度及患者年龄无关(P0.05);经Kaplan-Meier生存分析得出结果,胃癌患者中LOXL2蛋白表达阳性者的生存率均明显低于阴性者(P0.01);经相关性分析发现,LOXL2与PCNA、Cyclin D1、MMP-2、MMP-9蛋白表达具有正相关性(r=0.279,0.287,0.402,0.453;均P0.01)。结论在胃癌组织中LOXL2高表达,可能与PCNA、Cyclin D1、MMP-2、MMP-9具有协同促进作用,提高了胃癌发生发展、侵袭转移概率,可能是影响预后的危险因素。     

E-cadherin, beta-catenin, Cyclin D1在胃腺癌中的表达及临床意义

目的研究E-cadherin,β-catenin,Cyclin D1在胃腺癌组织中的表达,探讨三者的表达及临床病理意义.方法采用免疫组织化学SP法检测73例胃腺癌组织及18例正常胃黏膜组织中E-cadherin,β-catenin,Cyclin D1蛋白的表达.结果正常胃黏膜组织中E-cadherin和β-catenin均呈清晰的棕褐色染色在上皮细胞细胞膜.E-cadherin和β-catenin在胃癌细胞中出现细胞质和/或细胞核异常染色,其异常表达率分别为63.01%(46/73)和56.16%(41/73),且两者的异常表达与胃腺癌的分化程度、TNM分期、浸润深度及淋巴结转移相关,与患者的性别、年龄、肿瘤大小无关.胃腺癌中E-cadherin和β-catenin表达密切相关.Cyclin D1在胃腺癌组织中的阳性表达率为67.12%(49/73),明显高于其在正常胃黏膜组织中的表达(0%,0/18),且与胃腺癌的分化程度和淋巴结转移相关.E-cadherin和β-catenin在胃癌中的异常表达与Cyclin D1的过表达呈显著的正相关(r=0.249,r=0.376,P＜0.05).结论胃腺癌中存在E-cadherin和β-catenin基因的失活及蛋白表达下调.E-cadherin和β-catenin的异常表达可能通过促使或激活Cyclin D1的过表达而参与胃癌的发生和发展.     

Cyclin D1、p27在肺癌中表达的研究

目的研究Cyclin D1、p27基因蛋白在肺癌组织中的表达与肺癌临床病理特征的关系。方法：应用免疫组化S-P法检测109例手术切除肺癌组织标本中两种基因蛋白的表达。结暴：肺癌Cyclin D1基因过度表达的总阳性率为93.6%(102/109)。其中鳞癌为98%（50/51)，腺癌为97.2%（35/36），小细胞癌为77.3%(17/22);p27基因表达的阳性率为33%(36/109），其中麟癌为39.1%(20/51)，腺癌为25%(9/36），小细胞癌31.8%（7/22）。Cyclin D1阳性表达与肺癌的分化程度、TNM分期呈负相关。Cyclin D1和p27蛋白在肺癌组织中的表达呈负相关。结论：Cyclin D1和p27基因蛋白表达与肺癌发生、发展有关。     

Wnt信号通路的组件蛋白DKK-1、β-链接素及周期素D1蛋白表达与胃癌的相关性

目的探讨Wnt信号通路中的组件蛋白DKK-1、β-catenin及周期素(Cyclin)D1在胃癌的发生、发展及转移的相互关系。方法采用免疫组织化学方法标记DKK-1、β-catenin及Cyclin D1蛋白在80例胃癌组织标本,10例正常胃组织中的表达情况。结果 1DKK-1在胃癌组织中的表达明显低于胃正常组织(P0.05),高、中分化胃癌的表达高于低分化胃癌的表达(P0.05),伴有淋巴结转移的胃癌组织DKK-1较无转移病例阳性率低(P0.05)。2β-catenin在胃癌组织中的阳性表达率明显高于胃正常组织(P0.05),高、中分化胃癌的表达低于低分化胃癌的表达(P0.05),伴有淋巴结转移的胃癌组织β-catenin较无转移病例阳性率高(P0.05)。3Cyclin D1在胃癌组织中的表达明显高于胃正常组织(P0.05),高、中分化胃癌的表达低于低分化胃癌的表达(P0.05),伴有淋巴结转移的胃癌组织Cyclin D1较无转移病例阳性率较高(P0.05)。4在胃癌组织中DKK-1与Cyclin D1呈负相关关系(r=-0.453,P0.01),DKK-1与β-catenin呈负相关关系(r=-0.553,P0.01),Cyclin D1与β-catenin呈正相关关系(r=0.562,P0.05)。结论 Wnt信号通路中的组件蛋白DKK-1、β-catenin及Cyclin D1在胃癌的发生、发展及转移有一定的相互关系。     

胃癌组织中eIF4E、VEGF和Cyclin D1的表达及其意义

目的:研究胃癌组织中真核细胞起始因子4E(eukaryotic initiation factor 4E.eIF4E),血管内皮生长因子(vascular endothelial growthfactor,VEGF)和细胞周期素D1(Cyclin D1)蛋白的表达水平及其与临床病理的关系.方法:胃癌组织91例和正常胃黏膜组织30例采用免疫组织化学方法检测eIF4E,VEGF和Cyclin D1的表达,分析其表达差异,并结合其临床病理资料进行综合分析.结果:与正常胃组织相比,eIF4E,VEGF和Cyclin D1蛋白在胃癌组织中均呈高表达(95.6%,68.1%,84.6% vs 0.0%,均P＜0.01).eIF4E,VEGF和Cyclin D1的阳性表达率与患者的年龄、性别以及肿瘤分化程度均无明显相关性,但随着肿瘤浸润深度加深、淋巴转移产生、临床分期提高而升高(P＜0.05).eIF4E与VEGF,eIF4E与Cyclin D1的表达呈正相关(r=0.407,P＜0.05;r=0.780,P＜0.01).结论:eIF4E,VEGF和Cyclin D1的表达与胃癌的侵袭、转移密切相关,eIF4E表达与VEGF以及Cyclin D1显著相关.     

胃癌组织中CyclinD1和VEGF的表达及意义

目的　探讨 Cyclin D1 和 VEGF与胃癌分型、分期、浸润转移等生物学行为的关系及二者之间的相关性。方法　应用免疫组织化学链霉素抗生物素蛋白 -过氧化物酶法 (S- P)检测各期胃癌 (共 5 7例 )组织中Cyclin D1 和 VEGF的表达。结果　 Cyclin D1 表达与胃癌分化程度密切相关 ,与肿瘤浸润深度、淋巴结转移及TNM分期无关 ;VEGF的表达与胃癌的分化程度、肿瘤浸润深度、淋巴结转移、TNM分期均密切相关。在胃癌组织中 Cyclin D1 和 VEGF的表达呈正相关。结论　 Cyclin D1 过表达参与了胃癌的发生 ,VEGF促进胃癌的增长 ,促使肿瘤向黏膜深层浸润并向远处转移。Cyclin D1 和 VEGF在胃癌的发生中起协同作用 ,其表达与 TNM分期密切相关 ,二者联合检测可作为胃癌手术治疗及预后评估的参考指标     

Immunohistochemical expression of cell-cycle proteins in gastric precancerous lesions

Background: The early indicator for the subject predisposed to gastric cancer is abnormal proliferation of gastric epithelial cells, such as atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia, which have been considered as precancerous lesions of gastric cancer. To determine whether p53 protein, cyclins D1, and D3, and p27^kip1 play a role in the carcinogenesis pathway of gastric cancer, we performed an immunohistochemical study of their expression in gastric precancerous lesions. Methods: A total of 1 45 endoscopic gastric biopsy specimens of AG, IM, and gastric dysplasia were studied. These molecular markers were localized by immunohistochemistry. Results: P53 was expressed in 15% of cases with gastric dysplasia and not in the pre‐dysplastic stages of the gastric mucosa. All cases were concerning high‐grade dysplasia. Cyclin D1 protein was almost undetectable in the precancerous lesions of gastric cancer. Cyclin D3 protein overexpression was seen in 10% of biopsies with IM, and 50% of biopsies with gastric dysplasia. High expression of p27^kip1 protein was demonstrated in all cases of chronic gastritis. As atrophy, IM, and dysplasia develop, expression of p27^kip1 protein is suppressed. In total, 15% of dysplastic cases showed no expression of p27^kip1 protein. Conclusions: (i) P53 mutation must be a late event during the development of gastric cancer. (ii) Cyclin D1 protein overexpression may not play a role in the progression from normal to neoplastic gastric mucosa, while overexpression of cyclin D3 is an earlier event during gastric carcinogenesis, and its role must be further evaluated. (iii) Reduced expression of p27^kip1 is a rather early event in gastric tumorigenesis, before dysplastic changes occur.     

吲哚美辛对胃癌SGC 7901细胞增殖及Cyclin D1蛋白表达的影响

目的:观察引哚美辛对胃癌SGC 7901细胞增殖及细胞周期调控蛋白Cyclin D1表达的影响,探讨吲哚美辛抑制细胞增殖的机制.方法:采用MTT法观察吲哚美辛对胃癌细胞SGC 7901增殖的影响,采用流式细胞仪观察细胞周期分布的变化,采用免疫细胞化学方法检测Cyclin D1蛋白的表达.结果:吲哚美辛呈时间、浓度依赖方式抑制胃癌SGC 7901细胞增殖,改变细胞周期的分布,增加G0/G1期细胞的比例,下调Cyclin D1蛋白的表达.结论:吲哚美辛可能通过下调Cyclin D1蛋白表达,影响细胞周期的分布来抑制胃癌SGC7901细胞增殖.     

The role of overexpression and gene amplification of cyclin D1 in intrahepatic cholangiocarcinoma

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) is a primary liver malignant tumor with an extremely poor prognosis, but less attention has been directed to factors related to molecular carcinogenesis, including cell cycle proteins. We examined the expression and gene amplification of cyclin D1, the cell cycle regulating protein. Our objective was to evaluate correlations with clinicopathological factors in ICC. METHODS: Cyclin D1 overexpression and cellular proliferative activity (Ki-67 labeling index) were investigated immunohistochemically, and 20 cases were further investigated for cyclin D1 gene amplification, using differential PCR. We examined the correlation between the expression and gene amplification of cyclin D1 and clinicopathological factors, including overall survival in patients with ICC. RESULTS: Immunohistochemical analysis revealed an overexpression of cyclin D1 protein in 28 of 66 subjects with ICCs (42%). The cyclin D1 overexpression was associated with poor histological differentiation (P = 0.04), high cellular proliferative activity (P < 0.01), and a poor prognosis (P = 0.02) by univariate analysis, although it is not an independent prognostic factor by multivariate analysis. Cyclin D1 gene amplification was confirmed in five of the 20 patients. Of those five cases of ICC, all had poor histological differentiation, and four of the five ICCs (80%) showed evidence of cyclin D1 immunoreactivity. CONCLUSIONS: Overexpression and gene amplification of cyclin D1 are frequent and contribute to dedifferentiation and cellular proliferative activity of ICCs, and overexpression also indicates a poor prognosis for patients with ICC.     

胃癌组织cyclinE表达的临床病理意义

目的　Ｃｙｃｌｉｎ Ｅ 蛋白在细胞周期的Ｇ１ 晚期起作用,加速Ｇ１Ｓ期转化,与人类肿瘤有关． 本研究探讨ｃｙｃｌｉｎ Ｅ 蛋白在胃癌的意义．方法　用敏感而特异的免疫组化ＳＰ 法测定胃癌石蜡切片中ｃｙｃｌｉｎ Ｅ蛋白的异常表达．结果　Ｃｙｃｌｉｎ Ｅ 在胃癌中表达６２ ％ （ｎ ＝ ６０ ,Ｍ＝ ４３ ,Ｆ＝ １７ ,３２岁～７３ 岁） ,与癌旁组织２６ ％ 相比有显著差异（ Ｐ＜ ０－０５） ．Ｃｙｃｌｉｎ Ｅ表达与组织病理分化程度呈负相关． 分化差的胃癌组织ｃｙｃｌｉｎ Ｅ蛋白表达越强,ｃｙｃｌｉｎ Ｅ与肿瘤侵袭、淋巴结转移、远处转移无明显关系．结论　Ｃｙｃｌｉｎ Ｅ 蛋白与胃癌发生有关,与胃癌进展无关．ＣｙｃｌｉｎＥ 蛋白可做为胃癌的一个潜在的诊断和判断预后的指标．     

Alteration of cyclin D1 in gastric carcinoma and its clinicopathologic significance

AIM: To detect the genetic alteration and abnormal expression of cyclin D1 in gastric carcinoma and investigate its clinicopathologic significance in advanced gastric carcinoma. METHODS: Proteins of cyclin D1 were detected by immunohistochemistry in 42 cases of advanced gastric carcinoma with their follow-up data available, 27 cases of early stage carcinoma, 21 cases of gastric adenoma, 22 cases of hyperplastic polyp and 20 cases of normal mucosa adjacent to adenocarcinomas. Genetic alteration of cyclin D1 was detected by Southern blot and expression of cyclin D1 mRNA was detected by PT-PCR in 42 cases of advanced gastric carcinoma. RESULTS: Cyclin D1 protein was not expressed in normal mucosa, hyperplastic polyp and gastric adenoma, while it was only positively expressed in gastric carcinoma. The expression rate of cyclin D1 protein in early stage gastric carcinoma, advanced gastric carcinoma and lymph node metastasis was 48.1%, 47.4% and 50.0%, respectively. The amplification of cyclin D1 gene was detected in 16.6% of advanced gastric carcinomas. The overexpression of cyclin D1 mRNA was detected in 40.5% of the samples. There was no significant correlation between cyclin D1 protein expression and age, lymph-node metastasis and histological grading in patients with advanced gastric carcinoma (chi2 = 0.038, 0.059, 0.241, P>0.05). Significant correlation was observed between the expression of cyclin D1 protein and the 5-year survival rate (chi2 = 3.92, P<0.05). CONCLUSION: Detection of cyclin D1 protein by immunohistochemistry may be useful in the diagnosis of early gastric carcinomas. Patients with positive expression of cyclin D1 protein tend to have a worse prognosis.     

Overexpression of cyclin B1 in gastric cancer and its clinicopathological significance: an immunohistological study

PURPOSE: Cyclin B1 is a key regulator of progression through the G2/M transition during the cell cycle. Although cyclin B1 proteins are overexpressed in various types of human cancers, the relationship between cyclin B1 status in gastric cancer and its clinical significance remains unknown. METHODS: We examined cyclin B1 expression by immunohistological means in 61 patients with gastric cancer in terms of histological type, tumor invasion, and metastatic behavior. Specimens were considered positive when the cytoplasm of over 10% of the cancer cell population was stained. RESULTS: Cyclin B1 was overexpressed in 32 (53%) of 61 patients with gastric cancer. Tumors that expressed cyclin B1 were predominant in older patients, in well- and moderately differentiated adenocarcinomas and in expanding-growth type tumors. Conversely, expression of cyclin B1 was lower in poorly differentiated adenocarcinomas, and in those of the infiltrative growth type. Moreover, the disease was more advanced (stages III and IV) and widespread nodal involvement was more frequent when cyclin B1 expression was low. Logistic regression analyses showed that histological type is a significant factor related to cyclin B1 protein expression. CONCLUSIONS: These findings suggested that cyclin B1 protein overexpression is closely associated with less aggressive tumor behavior. Therefore, G2/M cyclin alternatives and the possible role of cyclins in cancer development warrants further attention.