Wnt1、β-catenin、APC和cyclin D1蛋白在胃癌中的表达

 目的检测Wnt1、β-catenin、APC和cyclin D1蛋白在胃癌中的表达情况。方法对45例人胃癌组织标本及肿瘤边缘5cm以外的正常组织进行LSAB免疫组织化学检测。结果45例胃癌组织中Wnt1、β-catenin、cyclin D1阳性率分别为57.78％、73.33％和51.11％,正常对照组织几乎不表达(β-catenin正常组织膜表达),相比差异有统计学意义（P<0.01）;APC 在GC（gastric carcinoma,GC）中表达的阳性率为（53.33%）,低于正常组织（91.11％）,差异具有统计学意义（P<0.01）。在同一胃癌标本中,Wnt1、β-catenin、cyclin D1同时高表达,即Wnt通路处于活化状态(Wnt+)占44.44％(20/45),正常组织未见激活状态（0/45）,差异具有统计学意义（P<0.01）。结论Wnt1-β-catenin APC-cyclin D1通路在胃癌发生过程中存在异常表达。     

β-catenin和cyclin D1在乳腺癌中的表达及意义

目的探讨乳腺癌组织中β－连接素(β-catenin)、细胞周期蛋白D1(cyclin D1)的表达与乳腺癌发生、浸润及转移的关系.方法应用SP免疫组化方法检测60例乳腺癌组织中β-catenin、cyclin D1的表达.结果乳腺癌组织中有42例(70％)β-catenin异常表达,28例(46.7％)cyclin D1过度表达.β-catenin异常表达率与乳腺癌大小、分化程度及淋巴结转移与否无显著相关性,P>0.05;β-catenin在Ⅲ～Ⅳ期乳腺癌、浸润性小叶癌中的异常表达率(90%、95%)明显高于Ⅰ～Ⅱ期乳腺癌、浸润性导管癌(60%、58.3%),P<0.05,P＜0.01.cyclin D1过度表达率与乳腺癌大小、组织学类型、分化程度无显著相关性,P>0.05;与TNM分期、淋巴结转移与否有显著相关性,P<0.05.β-catenin异常表达病例中,57.1％(24/42)的病例呈现cyclin D1的过度表达,但β-catenin正常膜表达病例中,22.2％(4/18)的病例呈现cyclin D1的过度表达.β-catenin异常表达与cyclin D1过度表达有显著的正相关性,rs=0.321,P<0.05.结论β-catenin的异常表达激活cyclin D1的过度表达,引起细胞增殖和分化失控,在乳腺癌的发生中可能起着重要作用.β-catenin的异常表达不是影响乳腺癌细胞转移的主要因素,但可能是一个协同因素.     

α,β-catenin和cyclin D1在乳腺癌中的表达及意义

目的探讨乳腺癌组织中α,β-连接素（α,β-catenin）、细胞周期蛋白D1（cyclin D1）的表达与乳腺癌发生、浸润及转移的关系。方法应用S-P免疫组化方法检测60例乳腺癌组织中α,β-catenin、cyclin D1的表达。结果乳腺癌组织中有37例（61.7％）α-catenin,42例（70％）β-catenln异常表达,28例（46．7％）cyclin D1过度表达。α,β-catenin异常表达率与分化程度及淋巴结转移与否无显著相关性（P〉0．05）;α,β-catenin在浸润性小叶癌中的异常表达率（85．7％、95％）明显高于浸润性导管癌（50％、58．3％）（P〈0．05）、（P〈0．01）。cyclin D1过度表达率与乳腺癌大小、组织学类型、分化程度无显著相关性（P〉0．05）;与TNM分期、淋巴结转移与否显著相关（P〈0.05）。β-catenin异位表达病例中,57．1％（24／42）的病例出现cyclin D1的过度表达,但β-catenin正常膜表达病例中,22．2％（4／18）的病例呈现cyclin D1的过度表达。β-catenin异常表达与cyclin D1过度表达有显著的正相关性（rn=0.321,P〈0．05）。结论 β-catenin的异常表达激活cyclin D1的过度表达,引起细胞增殖和分化失控,在乳腺癌的发生中可能起着熏要作用。α,β-catenin的异常表达不是影响乳腺癌细胞转移的主要因素,但可能是一个协同因素。     

E-cadherin和β-catenin在肝细胞癌中的表达及意义

[目的]探讨上皮型钙黏素（E-cadherin）和β-连环素（β-catenin）在肝细胞癌（HCC）中的表达及其与临床病理特征的关系。[方法]采用免疫组织化学方法检测61例HCC组织及其癌旁肝组织中E-cadherin和β-catenin蛋白的表达,分析其表达与HCC临床病理特征的关系。[结果]E-cadherin和β-catenin蛋白在癌组织中的异常表达率分别为34.43%和67.21%,而在癌旁肝组织中的异常表达率分别为14.75%和26.23%,癌组织与癌旁组织比较差异有显著性（P〈0.05）。E-cadherin表达与门脉癌栓、术后复发、肿瘤大小、肿瘤分化、肿瘤个数有关。β-catenin异常表达在不同肿瘤个数及不同肿瘤分化状况下差异有显著性。[结论]E-cadherin和β-catenin的异常表达可能与HCC的发生及术后的复发及转移有关,可能作为监测HCC恶性程度和判断预后的指标。     

应用组织芯片检测食管鳞状细胞癌中APC、β-catenin、E-cadherin与cyclinD1的表达及其意义

背景与目的：食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）的发生是个多因素多阶段的演进过程。Wnt信号转导通路在肿瘤发生发展中起重要作用。本研究探讨4种Wnt通路上的蛋白在食管鳞癌发生中的作用及在早期诊断中的意义。方法：制作由199例食管鳞癌组织与其癌旁164例正常粘膜、34例基底细胞增生和30例不典型增生上皮组成的组织芯片,应用免疫组化方法检测APC、 β-catenin、E-cadherin、cyclin D1的表达情况。结果：APC和E-cadherin在ESCC阳性率分别是69．6％、19．6％,均低于各自正常组（98．0％、96．3％,均为P〈0．01）, β-catenin和cyclin D1在ESCC的异常表达率分别是65．5％和70．9％,均高于各自正常组（1．2％,0．8％,均为P〈0．01）。按正常粘膜→基底细胞增生→不典型增生→ESCC的顺序,APC低表达发生在ESCC, β-catenin和E-cadherin表达异常始于不典型增生．cyclinD1过表达始于基底细胞增生。随着ESCC分化程度由高到低的改变,APC、E．cadherin和cyclinD1阳性率逐渐减少, β-catenin逐渐增加。 β-catenin的表达与APC无相关（r=-0．10,P〉0．05）,与E．cadherin呈负相关（r=-0．31,P〈0．01）,与cyclinD1呈正相关（r=0．49,P〈0．01）。结论：APC、E-cadherin、 β-catenin和cyclinD1可能在ESCC发生过程中起重要作用。 β-catenin、E-Cadherin和cyclinD1的表达检测有助于ESCC的早期诊断。     

APC、β-catenin、C-myc和Cyclin D1在大肠癌组织中的表达及其意义

背景与目的:Wnt信号转导通路成员各癌基因、抑癌基因的异常,激活下游相关靶基因的转录,在肿瘤发生发展中起重要作用.本研究通过检测不同大肠组织中APC、β-catenin、C-myc和Cyclin D1的表达情况,探讨其在大肠癌发生中的意义.方法:应用免疫组织化学方法检测30例正常大肠粘膜、30例大肠腺瘤、10例大肠腺瘤恶变及50例大肠癌组织中APC、β-catenin、C-myc和Cyclin D1蛋白的表达情况.以β-catenin在细胞膜表达为正常表达,而在胞浆和/或胞核表达为异位表达.结果:大肠癌和大肠腺瘤恶变组织APC阳性率分别为44.0%和40.0%,显著低于大肠腺瘤(86.7%)和正常大肠粘膜(100%)(P＜0.01).大肠癌、大肠腺瘤恶变组织和大肠腺瘤β-catenin胞浆和/或胞核异位表达率分别为62.0%、50.0%、30.0%,均显著高于正常大肠粘膜(0%)(P＜0.01),大肠癌β-catenin异位表达率显著高于大肠腺瘤(P＜0.01).大肠癌、大肠腺瘤恶变组织、大肠腺瘤中C-myc表达率分别为56.0%、60.0%、46.7%,均显著高于正常大肠粘膜(0%)(P＜0.01),而Cyclin D1阳性率分别为66.0%、60.0%、30.0%,均显著高于正常大肠粘膜(0%)(P＜0.01).大肠癌Cyclin D1表达率显著高于大肠腺瘤(P＜0.01).大肠癌中β-catenin异位表达与C-myc和Cyclin D1表达呈正相关关系(r=0.63,P＜0.01;r=0.57,P＜0.01),而与APC表达呈负相关关系(r=-0.39,P＜0.05).结论:大肠癌组织中存在APC低表达和/或β-catenin异位表达,以及C-myc和Cyclin D1的过度表达,4种基因蛋白可能在大肠癌发生过程中起重要作用.     

p65、β-catenin表达在乳腺癌发生、发展中的相关性分析

目的探讨p65、β-catenin表达在乳腺癌发生、发展中的相关性。方法采用免疫组化Envision法检测p65及β-catenin在不同病理阶段的乳腺组织中的表达状况。乳腺囊性增生病27例,导管内乳头状瘤25例,导管上皮异型增生26例,导管内癌（或伴早期浸润）29例,浸润性导管癌58例。结果p65和β-catenin在乳腺导管内乳头状瘤、囊性增生病、囊性增生病伴异型、导管内癌（或伴早期浸润）和浸润性导管癌中的阳性表达率分别为8.0%、11.1%、42.3%、31.0%、48.3%和4.0%、3.7%、23.1%、72.4%、79.3%。两者在良性增生性疾病阶段无明显相关性（P〉0.05）,在囊性增生病伴异型、乳腺导管癌阶段呈正相关（P〈0.05）。结论p65、β-catenin表达在乳腺增生性疾病无明显相关性,而在囊性增生病伴异型和乳腺癌中呈正相关。     

cyclin D1、pRb在大肠癌中的表达及其临床意义

目的研究大肠癌中cyclin D1和pRb的表达与临床病理参数之间的关系以及二者之间的关系.方法采用免疫组化方法S-P法检测67例大肠癌、40例癌旁粘膜和40例正常粘膜中cyclin D1和pRb的表达.结果大肠癌中cyclin D1和pRb的阳性率分别为44.8%和100.0%,明显高于癌旁粘膜和正常粘膜(P＜0.05),cyclin D1在低分化癌的过表达率高于高分化癌(P＜0.05),C+D期的过表达率明显高于A+B期(P＜0.01);pRb在C+D期的过表达率高于A+B期(P＜0.05),pRb的过表达率与肿瘤的分化程度无关(P＜0.05).相关分析表明,cyclinD1和pRb无明显相关(P＞0.05).结论cyclin D1参与了大肠癌的发生并与肿瘤的分化程度和Duke's分期有关,而pRb与肿瘤的分化程度无关.     

Significance of E-cadherin/beta-catenin complex and cyclin D1 in breast cancer

E-cadherin and beta-catenin are important epithelial adhesion molecules in normal epithelium. Loss of E-cadherin - beta-catenin adhesion is an important step in the progression of many epithelial malignancies. beta-catenin plays also a role in intracellular signaling and can function as an oncogene when binds to the T-cell factor 4 (Tcf4)-binding site in the promotor region of cyclin D1 and transactivates genes after translocation to the nucleus. We evaluated the immunohistochemical expression pattern of E-cadherin, beta-catenin in relationship with cyclin D1 overexpression, tumor stage, clinicopathologic parameters and patient survival in 128 mammary infiltrating duct carcinomas. The expression of E-cadherin/beta-catenin complex and beta-catenin/cyclin D1 double staining with confocal scanning laser microscope was evaluated. There were aberrant expressions in 78% of E-cadherin, 79% of beta-catenin, and 66% of cyclin D1 in breast cancer. There was correlation of aberrant expression of E-cadherin or beta-catenin with lymph node metastasis, survival rate, and survival length. However, there was no correlation of cyclin D1 overexpression with aberrant expression of E-cadherin or beta-catenin. No death was found in normal expression of beta-catenin, however lowest survival (50%) was found in nuclear beta-catenin expression. There was correlation of overexpression of cyclin D1 with survival rate and survival length. The highest survival rate and survival length were found in membranous normal beta-catenin expression group, however significant decrement of survival length was found in the groups of aberrant expression one or both of E-cadherin or/and beta-catenin. These results suggest that aberrant expression of E-cadherin, beta-catenin, and cyclin D1 may be involved in tumor metastasis, and analysis of the degree or the pattern of E-cadherin, beta-catenin, cyclin D1, and E-cadherin/beta-catenin complex may be good prognostic markers of mammary infiltrating duct carcinoma.     

E-cadherin and beta-catenin expression in breast medullary carcinomas.

The initial step of cancer invasion and metastasis is the escape of tumour cells from the primary site, involving disruption of normal cell-cell adhesion and E-cadherin (E-cad) and beta-catenin (beta-cat) down-regulation, as shown in various types of human malignancies including breast carcinomas. Medullary carcinomas are high grade and poorly differentiated tumours with syncytial typical pattern, and prognosis unexpectedly better than that in high grade breast carcinomas. In a series of 55 breast typical medullary carcinomas diagnosed according to the strict use of Ridolfi et al (Cancer 40: 1365-1385, 1977) criteria, E-cad and beta-cat were investigated using quantitative (SAMBA 2005 system) immunocytochemical assays on frozen sections. Results were compared to that obtained on paraffin sections and in a series (n=55) of grade 3 ductal carcinomas. It was shown that medullary carcinomas significantly (p<0.001) expressed more E-cad and beta-cat than grade 3 ductal carcinomas. E-cad and beta-cat correlated with high expression of P53, of c-erbB, and of Ki-67 antigens, and with lack of hormone receptors antigenic sites (p<0.001). It was concluded that favourable prognosis and syncytial pattern of typical breast medullary carcinomas likely results, at least partly, from a particular expression of cell-cell adhesion molecules, significantly limiting tumour growth and efficiently mastering the tumour cell dissemination, opposing to high proliferative activity (grade 3).     

α-、β-catenin和cyclin D1在乳腺癌中的表达及意义

Objective:To study the relationship between expressions of α-,β-catenins and cyclin D1 and the occurrence,infiltration and metastasis of breast cancer.Methods:High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-,β-catenins and cyclin D1 in the 60 cases of breast cancer tissues.Results:Abnormal immunoreactivities of α- and β-catenins were observed in 37(61.7%)and 42(70%)cases of breast Cancer tissues,respectively.There were 28 cases(46.7%)who showed cyclin D1 overexpression.The abnormal expression rates of α -and β-catenins in infiltrating lobular carcinoma(ILC)were significantly higher than those in infiltrating ductal Carcinoma(IDC)(P＜0.05),but they had no relations to the extenl of differentiation and lymphatic metastasis of breasl Cancer(P＞0.05).The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer(P＜0.05),but not with histological type and lhe extent of differentiation(P＞0.05).Cyclin D1 overexpression was observed in 57.1%(24/42)of these cases that showed abnormal staining of β-catenin,but only observed in 22.2%(4/18)of these cases with normal membranous staining of β-catenin.There was a significantly positive correlation between the abnormal expression of β-catenin and overexpression of cyclin D1(rs=0.321.P＜0.05).Conclusion:The abnormal expression of β-Catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression in breast cancer.The abnormal expressions of α- and β-catenins are not a key factor in malignant cell metastasis in breast cancer,but may also involve in the progress.     

The expressions and significance of α-, β-catenins and cyclin D1 in breast cancers

Objective  To study the relationship between expressions of α-, β-catenins and cyclin D1 and the occurrence, infiltration and metastasis of breast cancer. Methods  High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-, β-catenins and cyclin D1 in the 60 cases of breast cancer tissues. Results  Abnormal immunoreactivities of α-and β-catenins were observed in 37 (61.7%) and 42 (70%) cases of breast cancer tissues, respectively. There were 28 cases (46.7%) who showed cyclin D1 overexpression. The abnormal expression rates of α-and β-catenins in infiltrating lobular carcinoma (ILC) were significantly higher than those in infiltrating ductal carcinoma (IDC) (P < 0.05), but they had no relations to the extent of differentiation and lymphatic metastasis of breast cancer (P > 0.05). The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer (P < 0.05), but not with histological type and the extent of differentiation (P > 0.05). Cyclin D1 overexpression was observed in 57.1% (24/42) of these cases that showed abnormal staining of β-catenin, but only observed in 22.2% (4/18) of these cases with normal membranous staining of β-catenin. There was a significantly positive correlation between the abnormal expression of β-catenin and overexpression of cyclin D1 (r _s = 0.321, P < 0.05). Conclusion  The abnormal expression of β-catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression in breast cancer. The abnormal expressions of α-and β-catenins are not a key factor in malignant cell metastasis in breast cancer, but may also involve in the progress.     

Cytologic evaluation of cyclin D1 expression in primary breast carcinoma

BACKGROUND: Preoperative assessment of the biologic characteristics of primary breast carcinoma is important because neoadjuvant medical therapy is being used increasingly. In the current study, the authors attempted to evaluate the validity of cyclin D1 assay in fine-needle aspiration (FNA) samples from patients with primary breast carcinoma. METHODS: FNA samples were obtained prior to therapy and multiple slides were stored at -80 degrees C for subsequent immunocytochemical analysis (ICA). ICA for cyclin D1 protein was performed on FNA samples from 51 breast carcinoma patients and 20 samples from patients with benign breast disease. In 45 breast carcinoma patients who had undergone surgery, sections were taken from paraffin blocks and stained by ICA for cyclin D1 validation. Possible correlations between cyclin D1 expression in the FNA samples and the biologic data of the patients also were analyzed. RESULTS: Cyclin D1 expression was detected in 37 FNA samples from 51 breast carcinomas (72.5%) whereas expression of cyclin D1 was detected in 8 FNA samples from 20 patients with benign breast disease (40%). In histologic sections after surgery, 26 cases of breast carcinoma (65%) showed a positive reaction to cyclin D1. Concordance for the presence of cyclin D1 between FNA samples and histologic samples was 75%. Cyclin D1 expression was high in patients with the tumors that expressed estrogen receptor (ER) (30 of 34 vs. 5 of 11; P = 0.028) and progesterone receptor (PR) (33 of 38 vs. 2 of 7; P = 0.007). There was no significant relation found between cyclin D1 expression and tumor size or lymph node metastasis. Cyclin D1 expression within invasive ductal carcinoma was observed in > 80% of low or intermediate nuclear grade tumors but its expression decreased to 61.5% (8 of 13 cases) in tumors with high nuclear grade (P = 0.023). All 14 breast carcinomas in which the S-phase fraction was 15% showed cyclin D1 expression. Cyclin D1 expression was found to be correlated inversely with proliferative activity in breast carcinoma (P = 0.023). CONCLUSIONS: The results of the current study show that cyclin D1 expression can be measured by ICA in FNA samples with reasonable concordance with the results of histologic section. Cyclin D1 expression was found to be associated with ER/PR status and cell differentiation. The results of the current study indicate that the measurement of novel molecular markers could be performed adequately in FNA samples as well as in histologic sections.     

Expression of cyclin E and cyclin D1 in non-small cell lung cancers

The relationships between overexpression of cyclin D1 or cyclin E and clinicopathological factors were investigated in 157 patients with non-small cell lung cancers (NSCLCs) using immunohistochemical analysis. Fifty-eight cases of NSCLCs (58/157, 37%) showed the overexpression of cyclin D1, and 64 cases (64/157, 41%) were positive for cyclin E. Cyclin E and cyclin D1 were infrequently concurrently overexpressed (17/157, 10.8%). Overexpression of cyclin E was more frequently observed in squamous cell carcinoma (29/57, 51%) compared with that in adenocarcinoma (28/86, 33%) (P<0.05). In addition, overexpression of cyclin E was more frequently observed in poorly or moderately differentiated NSCLCs (52/103, 50%) than in well-differentiated ones (12/54, 22%) regardless of their histological types (P<0.01). On the contrary, there was no statistically significant relationship between cyclin D1 overexpression and histological types or grade of tumor differentiation. These findings suggest that expression of cyclin E was frequently independent of that of cyclin D1 and played some roles in the grade of tumor differentiation in NSCLCs.