β-catenin 在肝癌组织中的 表达及对肝癌患者预后的影响

目的：探讨β-catenin在肝细胞癌（HCC）组织中的表达及其与肝癌预后的关系。方法：用免疫组织化学方法检测83例HCC、26例癌旁组织和5例正常肝组织中β-catenin蛋白的表达情况,并对行肝癌根治性术患者进行术后随访,分析β-catenin蛋白表达与临床因素、HCC病理分化程度及患者术后生存的关系。结果：β-catenin蛋白在HCC、癌旁组织及正常肝组织中的阳性表达率分别为68.67%（57/83）、30.77%（8/26）和20%（1/5）,其在HCC中的表达阳性率高于正常肝组织及癌旁组织（P < 0.05）;β-catenin阳性表达率与肝癌病理分化程度呈负相关（r=-0.34,P=0.027）;有效随访68例,在随访的5年内,β-catenin阳性表达组平均生存时间11.2个月,β-catenin阴性表达组平均生存时间26.6个月,Kaplan-Meier生存分析表明β-catenin阴性表达患者比阳性表达患者术后生存更长,Log-Rank检验两组预后有显著性差异（χ²=15.138,P=0.000）。结论：β-catenin与HCC分化程度相关,β-catenin在肝癌组织中的高表达提示患者预后不良。     

乳腺癌组织β-catenin表达及与预后关系的分析

目的:分析β-catenin在乳腺癌组织中的表达特点及与预后的关系,以寻找新型的乳腺癌预后标志。方法:用组织芯片及免疫组织化学的方法检测β-catenin在213例乳腺癌组织中的表达,采用ROC曲线确定β-catenin表达高低的分界值,采用单变量及多变量分析β-catenin表达与乳腺癌预后的关系。结果:213例乳腺癌患者中,71.4%(152/213)为β-catenin高表达,28.6%(61/213)为β-catenin低表达;单变量分析显示,β-catenin高表达的患者总生存率(P=0.003)、无进展生存率(P=0.040)及无远处转移生存率(P=0.024)均低于β-catenin低表达的患者;多变量分析显示,β-catenin与乳腺癌患者总生存率(RR=5.961,95%CI:0.238～0.855,P=0.015)和无远处转移生存率(RR=3.888,95%CI:0.269～0.996,P=0.049)相关。结论:乳腺癌患者中β-catenin呈高表达,且表达越高预后越差。β-catenin可作为判断乳腺癌预后的一个新型、独立的指标。     

The prognostic significance of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study of 121 Arab patients

BACKGROUND: The variability of prognosis within a pathological stage of gastric cancer (GC) at presentation, underscores the need for specific biological markers to identify subgroups of patients with aggressive course for intensive treatment. To our knowledge, this is the first study from an Arab population reporting on the relationship of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 expression, and clinicopathological features and their prognostic significance. METHODS: Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67. The results were correlated with clinicopathological features and survival. RESULTS: M:F = 80:41; median age = 60 years; stage III and IV = 71%; and median follow-up = 34.4 months. Positive expression rates of p53, p27 kip1, p21 waf1, Ki67, and HER-2/neu were 54%, 40%, 8.3%, 70%, and 12% respectively. p53 expression correlated with age <60 years (P = 0.03), tumor size >5 cm (P = 0.01), p27 kip1 and Ki67 expression (P = 0.0001), and HER-2/neu (P = 0.04). p21 waf1 correlated inversely with T-stage (P = 0.008) and Her-2/neu expression correlated with histological grade (P = 0.04) and T-stage (P = 0.008). Univariate analysis showed that p53 overexpression (P = 0.01), fungating and infiltrative macroscopic appearance (P = 0.02), size >5 cm (P = 0.0001), lymph node metastasis (P = 0.0001), p T3 and T4 disease (P = 0.01), and overall stage III and IV (P = 0.0001) disease were adverse prognostic factors. Patients with tumor profiles p53 (-)/p27 (+) had better survival than those with p53 (+)/p27 kip1 (-)(P = 0.02). On multivariate analysis by Cox regression model, the expression of p53 (P = 0.03) and lymph node involvement (P = 0.01) were significant adverse prognostic factors for overall survival. CONCLUSIONS: The expression of p53 in Arab patients with GC correlates with aggressive tumor characteristics and is an independent prognostic factor. The combined analysis of p53 and p27 kip1 is of added prognostic value.     

AR和β-catenin在肝细胞癌中的表达及其临床意义

目的:探讨AR和β-catenin在肝细胞癌中的表达情况及其临床意义.方法:应用细胞侵袭及迁移实验检测AR基因沉默后对肝癌细胞株97H侵袭及迁移能力的影响;应用Western-blot实验在蛋白水平检测AR基因沉默后β-catenin的变化;应用免疫组织化学方法检测80例肝细胞癌组织中AR和β-catenin的分布,并分析与临床病理参数及患者生存率间的关系.结果:细胞侵袭、迁移实验显示,AR基因沉默后抑制肝癌细胞株97H的侵袭与迁移能力(P<0.01);AR基因沉默后可下调核β-catenin的表达;AR和核β-catenin过表达患者明显比低表达患者有更低的总体生存率(P<0.01);多因素分析显示AR、β-catenin是肝细胞癌独立的预后因素.结论:AR可能通过调节核β-catenin的表达来促进肝癌细胞侵袭和迁移;AR和β-catenin过表达与肝细胞癌患者不良预后明显相关.     

干细胞标志物SOX-2、β-catenin表达与胃癌术后复发转移关系

背景与目的：胃癌术后复发转移严重影响患者生存情况,SOX基因是经典Wnt信号通路的调控因子,其在胃癌术后复发及转移过程中可能发挥重要作用。本研究旨在探讨胃癌术后复发、远处转移患者肿瘤组织中SOX-2、β-catenin表达情况,探讨两者在胃癌术后复发及转移的作用。方法：采用免疫组化方法检测71例经手术切除胃癌患者的肿瘤组织中SOX-2和β-catenin蛋白表达情况,并分析其与临床病理特征和无病生存时间(disease free survival,DFS)的关系。结果：SOX-2在胃癌中的表达与胃癌复发转移、淋巴结浸润及分化程度有关(P=0.011,P=0.036,P=0.034),与患者性别、年龄及T分期无关。β-catenin在胃癌中的表达与胃癌复发转移、淋巴结浸润及T分期有关(P=0.025,P=0.014,P=0.026),与分化程度、患者性别及年龄无关。且二者均呈阳性表达者其术后复发转移率高于任意单阳性者,复发转移率分别为84%(21/25)和66.7%(24/36),二者均阴性表达者其复发转移率为30%(3/10)。生存分析显示SOX-2和β-catenin的表达与患者DFS相关。结论：SOX-2、β-catenin表达可能是胃癌术后复发转移有效的预测因子,两者联合检测有利于预测胃癌患者术后复发转移。     

CD147, MMP-2, MMP-9 and MVD-CD34 are significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients

OBJECTIVE: The prognostic role of tumor biological markers (biomarkers) in predicting recurrence of hepatocellular carcinoma (HCC) was investigated in this study, the results of which may help to select appropriate candidates for liver transplantation (LT). METHODS: Tissue samples from 82 HCC patients with cirrhosis who had undergone LT were immunohistochemically stained with antibodies of anti-CD147, anti-matrix metalloproteinases-2 (MMP-2), MMP-9 and anti-vascular endothelial growth factor (VEGF). Tumor microvessel density (MVD) was evaluated by using CD34. Multivariate Cox regression analysis was performed to identify the relevant prognostic factors. RESULTS: A significant correlation was found between the expression of CD147, VEGF, MMP-2, MMP-9 and MVD-CD34 in HCC. Tumor CD147 expression (P < 0.0001), tumor MVD-CD34 (P < 0.0001), MMP-9 in stromal compartment (P = 0.0257) and tumor VEGF expression (P = 0.0335) were significantly associated with the recurrence in HCC patients after LT. Univariate analysis showed that strong CD147 expression and high MVD-CD34 were significantly associated with poor tumor recurrence-free survival after LT (P < 0.0001). Multivariate analysis indicated that CD147 (P = 0.0001), MVD-CD34 (P = 0.0118), MMP-2 (P = 0.0312) and MMP-9 (P = 0.0280) in stromal compartment were all significant predictors in predicting HCC recurrence, while VEGF, MMP-2 and MMP-9 in tumor compartment were not significantly associated with poor prognosis. CONCLUSIONS: The tumor biomarkers CD147 and MVD-CD34 are more feasible markers for rational selection of LT candidates with HCC. MMP-9 and MMP-2 expression in stromal compartment, combined with pTNM tumor grade, may be helpful in predicting poor prognosis in HCC patients after LT.     

Clinical Significance of TRIM44 Expression in Patients with Gastric Cancer

Background: Despite the tremendous efforts in finding a valuable markers for risk stratifying gastric cancer (GC) patients; still, management of this cancer faces multiple obstacles. Given this, we designed a study to explore the possible relationship between the tripartite motif-containing 44 (TRIM44) gene expression, and the outcome of the GC patients. Methods: The real-time quantitative PCR method was used to evaluate the mRNA expression level of TRIM44, and β-catenin in fresh primary tumor and adjacent normal tissues collected from 40 GC patients. The Pearson’s correlation test, Kaplan–Meier method, and Cox proportional-hazards regression were performed to examine the association of TRIM44 expression with some clinicopathological data and the patients’ overall survival (OS). Results: The expression level of both TRIM44 and β-catenin was remarkably higher in GC tissues than in normal tissues (Fold change=1.71, p=0.004). In subgroup analysis based on the TRIM44 expression, pateints with high TRIM44 expression level exhibited poorer overall survival (HR = 1.46, 95% CI: 1.07-1.98, p=0.016). More strikingly, a positive correlation was also found between the expression of TRIM44 and β-catenin in GC, indicating that TRIM44 might exert its oncogenic activities probably through the β-catenin axis. Conclusion: This study highlighted the potent value of TRIM44 as an independent prognostic factor in gastric cancer and shed light on the probable interplay between this tripartite motif-containing protein and β-catenin. However, further investigations, especially with a larger sample size, are required to study the effect of TRIM44 in GC more precisely.     

β-catenin和Nanog表达与结肠癌术后复发转移的相关性分析

目的:探讨结肠癌组织中β-catenin和Nanog表达及其对复发转移的预测作用.方法:采用免疫组化方法检测80例结肠癌组织β-catenin和nanog表达,RT-PCR检测20例冷冻标本肿瘤及癌旁组织中Nanog表达.结果:在80例患者中,35例出现复发转移,β-catenin和Nanog在转移组中表达率分别为65.7％(23/35)和60.0％(21/35),在非转移组中分别为31.1％(14/45)和26.7％(12/45),差异有统计学意义(x2=9.483,P=0.002;x2 =9.026,P=0.003).结肠癌原发灶分化程度不同,β-catenin和Nanog表达存在差异,但是同T和N分期没有明显联系.生存分析结果显示,不同表达状态其远处转移出现时间差异有统计学意义(P=0.000 2),两者均为阳性表达其转移率明显高于均为阴性表达.RT-PCR分析下结果显示,20例肿瘤组织中Nanog阳性表达率为35.0％(7/20),明显高于癌旁组织,P=0.018.结论:肿瘤组织中β-catenin和Nanog表达同结肠癌术后复发转移发生相关,两者联合检测有助于评估肿瘤转移的可能.     

Loss of p27Kip1 expression is a strong independent prognostic factor of reduced survival in N0 gastric carcinomas

BACKGROUND: p27KiP1 is a cyclin-dependent kinase inhibitor and is a potential tumor suppressor gene. Reduced expression of p27Kip1 is a powerful negative prognostic marker in primary lung, breast, colon, bladder, and prostate carcinomas. In the current study, the prognostic value of p27Kip1 in gastric cancer was evaluated and compared with other histopathologic parameters and p53 expression. METHODS: p27Kip1 and p53 protein expression were determined by immunohistochemistry in 96 gastric carcinomas. The tumors were from a low incidence population and were selected for the absence of lymph node involvement. RESULTS: Reduced expression of p27KiP1 (< or = 50% positive cells) and nuclear p53 accumulation (> 30% positive cells) were observed in 67 (69.8%) and 9 (9%) tumors, respectively, and were not related to either the pT category or tumor histology. Kaplan-Meier analyses revealed a significant impact on survival by p27Kip1 (P = 0.0001 by log rank test), p53 (P < 0.0001) expression, and the pT category (P < 0.0001). On multivariate analysis, reduced p27Kip1 protein expression was the strongest independent predictor of reduced survival (P = 0.005; relative risk = 3.348) out weighing the pT category (P = 0.010; relative risk = 2.257) and p53 overexpression (P = 0.016; relative risk = 2.618). CONCLUSIONS: These data indicated that immunohistochemical detection of p27Kip1 could help to identify gastric carcinoma patients who are at high risk of death, even in the absence of lymph node involvement, and who might benefit from an adjuvant treatment following surgery.     

Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma

BACKGROUND: Inactivation of the tumor suppressor gene PTEN/MMAC1/TEP1, located on chromosome 10q23, is a common event in advanced stages of diverse human malignancies. However, the prognostic role of PTEN expression in patients with hepatocellular carcinoma (HCC) has not been characterized. METHODS: One hundred five resected specimens were collected from patients with HCC. Expression levels of PTEN and p53 in clinical samples were analyzed by immunohistochemistry. RESULTS: Immunohistochemical analysis of 105 HCC tissue specimens revealed that decreased or absence of PTEN immunostaining was found in 43 specimens (40.9%). Reduced PTEN expression levels were correlated with increased tumor grade (P = 0.017), advanced disease stage (P = 0.016), and elevated serum alpha-fetoprotein (alphaFP) levels (P = 0.001). Kaplan-Meier analysis indicated that patients with reduced PTEN levels had shorter overall survival (P = 0.001) and higher recurrence rates (P = 0.0007) compared with patients who had intact PTEN expression. Examining p53 expression unveiled an inverse correlation between p53 overexpression and reduced PTEN expression in patients with HCC (P = 0.004). In addition, patients with p53 overexpression had shorter overall survival compared with patients who were without p53 overexpression (P = 0.0014). Univariate and multivariate analyses revealed that reduced PTEN expression was an independent prognostic factor for survival in patients with HCC. CONCLUSIONS: The current study demonstrated that reduced PTEN expression levels are involved in the pathogenesis of HCC. Moreover, decreased PTEN expression was correlated with tumor progression, high alphaFP levels, p53 overexpression, and poor prognosis in patients with HCC.     

Angiogenesis, p53, and c-erbB-2 immunoreactivity and clinicopathological features in male breast cancer

BACKGROUND AND OBJECTIVES: p53, c-erbB-2, and tumor microvascular density have been shown to be potential prognostic tools in female breast cancer. Our objective was to assess the significance of these biomarkers as prognostic factors in infiltrating male breast cancer. METHODS: A retrospective study of expression of p53, c-erbB-2, and tumor microvascular density was done on a group of 26 male breast cancer patients. Biotin-streptavidin immunohistochemical study with specific anti-p53, anti-c-erbB-2, and anti-CD34 antibodies was carried out on paraffin sections of breast carcinoma. The data of expression of the biomarkers were merged with clinicopathological data such as tumor grade, T class, TNM stage, estrogen receptor status, tumor recurrence, and patient survival. RESULTS: p53 and c-erbB-2 were expressed in 46% and 39% of carcinomas, respectively. No correlation was found between positive immunoreactivity of p53, and tumor grade, size, T class, TNM stage, and survival. Nor was any relation found between tumor size, T class, TNM stage, survival, and c-erbB-2 overexpression. c-erbB-2 overexpression was significantly higher in high grade carcinomas. Estrogen receptor (ER) were positive in 21 out of 26 of tumors (81%). No trends were observed between estrogen receptor status and clinicopathological parameters or survival (data not shown). There was a positive correlation between mean microvascular density (MVD), advanced T class, and survival: higher MVD counts were found in patients with advanced tumors and in those who had tumor relapses or died of metastatic disease. CONCLUSIONS: This study suggests that tumor microvascular density may serve as a potential prognostic tool in male breast carcinoma.     

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。     

转录因子SOX2在胃癌中的表达及其临床意义

目的 探讨转录因子SOX2在胃癌组织中的表达情况及其与临床病理特征的关系.方法 应用免疫组织化学技术检测67例胃癌组织中SOX2的表达,并选取30例远端切缘胃壁组织作为对照.结果 SOX2在胃癌组织中的阳性表达率为52.24％（35/67）,显著低于对照组胃壁组织的阳性表达率93.33％（28/30）,差异有统计学意义（χ^2=16.326,P＜ 0.01）;在胃癌组织中SOX2的阳性表达率与肿瘤的分化程度、浸润深度、淋巴结转移以及临床分期有关,差异均有统计学意义（均P＜ 0.05）.结论 SOX2表达下调与胃癌的早期发生有关,并与淋巴结转移及TNM分期密切相关,SOX2可作为预测胃癌预后的生物学指标.     

E-cadherin、β-catenin及p120在上皮性卵巢癌中的表达及临床病理意义

目的:探讨黏附复合体相关蛋白E-cadherin、β-catenin及p120在人类卵巢癌组织中的表达及其与患者临床病理特征及预后的关系.方法:采用免疫组织化学染色法检测281例卵巢癌患者肿瘤组织中E-cadherin、β-catenin及p120的表达水平,分析其与临床病理特征之间的关系,比较其在卵巢癌原发灶与转移灶之间的差异.结合患者随访资料,利用Kaplan-Meier法绘制生存曲线,Log-rank法分析E-cadherin、β-catenin或p120的表达水平与卵巢癌患者预后的关系,COX回归模型分析卵巢癌患者预后的独立预测因素.结果:β-catenin在卵巢癌原发灶与转移灶间表达水平具有统计学差异(P=0.018),卵巢癌组织中p120的表达水平与患者FIGO分期(P=0.043)、组织学类型(P＜0.001)、肿瘤分级(P ＜0.001)有关,Spearman法分析证实E-cadherin与β-catenin(P=0.005)、β-catenin与p120(P ＜0.001)、E-cadherin与p120(P ＜0.001)具有相关性,卵巢癌组织中β-catenin(P=0.008)及p120(P =0.006)低表达的患者较高表达者总生存期缩短,多因素分析发现FIGO分期、β-catenin或p120表达水平是卵巢癌患者总生存期的独立预测因素.结论:鉴于黏附复合体在卵巢癌发生、浸润及转移中均发挥了重要作用,综合评估其相关蛋白E-cadherin、β-catenin及p120的表达水平,有助于判断卵巢癌的生物学行为及预测患者的预后.     

p53 and β-Catenin Expression Predict Poorer Prognosis in Patients With Anaplastic Large-Cell Lymphoma

BackgroundThe Wnt/β-catenin signaling pathway is a major target of p53. β-Catenin/p53 coexpression predicts poorer survival in carcinoma patients. Conversely, CD99 inhibits tumor metastasis through the Wnt/β-catenin pathway. We therefore assessed p53, β-catenin, and CD99 by immunohistochemistry.Patients and MethodsWe studied 45 patients with systemic anaplastic large-cell lymphoma (ALCL), including 20 anaplastic lymphoma kinase (ALK)-positive and 25 ALK-negative ALCL. β-Catenin expression was analyzed using phospho-β-catenin-S552 antibody because its nuclear localization indicates Wnt signaling.ResultsIn this cohort, p53 expression was associated with ALK-negative ALCL. Furthermore, p53 or β-catenin expression alone or β-catenin/p53 double expression showed poorer overall survival and disease-free survival in patients with ALCL overall and in patients with ALK-negative ALCL. CD99 expression was more frequent in ALK-positive ALCL but had no prognostic significance.ConclusionThis is the first study to evaluate phospho-β-catenin-S552 expression in ALCL. The results of this study, although limited by small patient size, suggest that β-catenin and p53 may play a role in pathogenesis and may be helpful in risk stratification of ALCL patients.     

Twist、E-cadherin和β-catenin在肝细胞肝癌中的表达及其与预后的关系*

目的:探讨Twist、E-cadherin 和β-catenin 在肝细胞肝癌复发与转移中的作用及与预后的相关性。方法:以石蜡包埋组织切片,免疫组化SP法染色分别检测97例肝细胞肝癌,其中复发与转移组49例,非复发与转移组48例Twist、E-cadherin 和β-catenin 的表达情况。结果:复发、转移与性别、年龄无关（P=0.424,P=0.738）,与临床分期密切相关（P=0.000）。 复发与转移组Twist、β-catenin 表达高于无复发与转移组（P=0.000;P=0.000）,复发与转移组E-cadherin 表达低于无复发与转移组（P=0.027）。Twist,β-catenin 阳性组平均生存时间分别为（28.880 ± 3.285）、（ 31.477 ± 3.359）个月,中位生存时间分别为26、28个月,阴性组平均生存时间分别为（44.603 ± 3.521）、（ 42.009 ± 3.720）个月,中位生存时间分别49、45个月,Twist、β-catenin 阳性组生存期较阴性组缩短差别具有统计学意义（P=0.002,P=0.029）。 E-cadherin 阳性组平均生存时间为（44.514 ± 3.447）个月,中位生存时间为49个月,阴性组为（29.110 ± 3.581）个月,中位生存时间为25个月,E-cadherin 阳性组生存时间较阴性组延长有统计学意义（P=0.002）。 结论:Twist、β–catenin 过度表达,E-cadherin 表达缺失可能与HCC 复发转移、不良生存预后存在相关性。