AKT2 expression in histopathologic grading and recurrence of meningiomas

Background

AKT2 (protein kinase B), an important protein in PI3K signaling pathway, is overexpressed in a variety of malignant tumors. However, in patients with meningiomas, the potential correlation between AKT2 and clinical outcome remains unknown.

Methods

The expression of AKT2 and Ki-67 in meningioma tissues were evaluated immunohistochemically in 94 patients with meningiomas. The correlation of AKT2 immunoreactivity with clinicopathological features and the prognostic value of AKT2 in patients were also analyzed.

Results

In this study, we examined the expression of AKT2 in meningiomas and unveiled its possible relationship with the clinical outcome. Immunohistochemical analysis revealed high AKT2 expression in 46 patients (46/94, 48.9%) and low AKT2 expression in the remaining 48 patients (48/94, 51.1%). There was a positive correlation between AKT2 and Ki-67 immunoreactivity (r = 0.35, P = 0.01). Clinicopathological evaluation suggested that AKT2 expression was associated with pathological grade and recurrence (P < 0.05). Univariate and Cox analysis indicated a significant correlation between high levels of AKT2 immunoreactivity and high rates of tumor recurrence (P < 0.05).

Conclusions

We conclude that AKT2 may play an important role in the development of meningioma. High AKT2 labeling index indicates higher grade of meningioma, and therefore AKT2 may be a useful molecular marker for predicting the prognosis of meningioma.     

Ki-67、c-myc、p53在食管癌中的表达及其意义

目的 探讨Ki-67、c-myc、p53在食管癌中的表达及其意义.方法 选取食管癌标本25例、切缘远端正常组织标本25例,采用免疫组织化学法检测组织中Ki-67、c-myc、p53蛋白的表达情况.结果 食管癌组织中Ki-67、c-myc、p53中位表达量分别为5.0、2.0、3.0,明显高于癌旁正常组织的1.0、0.5、0.3（均P＜0.05）.高分化食管癌组织Ki-67中位表达量（3.0）低于中低分化组（6.0）,差异有统计学意义（P＜0.05）.食管癌组织Ki-67与c-myc的表达呈正相关（P＜0.05）.结论 食管癌组织中Ki-67、c-myc、p53高表达,且随分化程度升高而升高,Ki-67、c-myc、p53有望成为食管癌的肿瘤标志物.     

Determination of proliferative fractions detected by immunohistochemistry with the monoclonal antibodies to bromodeoxyuridine and Ki-67 in malignant lymphomas

The stainability of proliferating cells with monoclonal antibodies to both bromodeoxyuridine (BrdU) and Ki-67 were compared in 22 malignant lymphomas and six related conditions. A significant correlation was observed (r = 0.78) between the positivities of proliferating cells determined using these two monoclonal antibodies. The growth fractions determined with the antibodies were usually related to the histologic classification, but labelling index was more varied in diffuse large cell type lymphoma. BrdU labelling was well correlated with the Working Formulation, and more useful as a prognostic indicator. On the other hand, Ki-67 was useful for broad recognition of cell proliferative ability.     

Bmi-1、Ki-67在黑色素瘤中的表达及其意义

目的:探讨Bmi-1、Ki-67蛋白在黑色素瘤(MM)中表达及其意义.方法:采用SP免疫组化法分别检测35例黑色素瘤和14例皮内痣组织石蜡切片中Bmi-1、Ki-67蛋白的表达情况,并对Bmi-1、Ki-67行相关性分析.结果:在黑色素瘤中,Bmi-1蛋白阳性表达率与皮内痣相似(P ＞0.05),但中高阳性表达率明显高于皮内痣组(P＜0.05);Ki-67蛋白阳性及中高阳性的表达率均较皮内痣组明显增强(P＜0.01);Bmi-1蛋白中高阳性表达与病理分级密切相关(P＜0.05);Ki-67蛋白中高阳性表达与患者有无淋巴结转移密切相关(P＜0.05);Ki-67与Bmi-1的表达呈正相关(P＜0.01).结论:Bmi-1、Ki-67蛋白表达与黑色素瘤的发生及预后关系密切,可作为评估患者肿瘤性质及预后的参考指标.     

The clinical value of Ki-67/MIB-1 labeling index in human astrocytomas

The current WHO classification of human astrocytomas has limitations in predicting prognosis and diagnosis, and there is a need for additional factors. Several studies have investigated the clinical value of proliferative activity in these tumors, especially the Ki-67/MIB-1 labeling index (LI). The aim of this study was to review the literature on this topic to get a survey of the current experience. All studies show increasing values of Ki-67/MIB-1 LI with increasing grade of malignancy. Most of them demonstrate that MIB-1 LI differentiates well between diffuse astrocytomas WHO grade II (AII) and anaplastic astrocytomas (AA) and between AII and glioblastomas (GM), but not between AA and GM. There is, however, considerable overlap of indices between the different malignancy groups. Further, in most studies positive correlations between MIB-1 LI and survival are found, though the proposed cut-off values vary substantially between the reports. The studies reviewed report MIB-1 LI as an important prognostic factor in human astrocytomas. Due to the great spread of values between the various tumor grades, however, MIB-1 LI cannot be used as a diagnostic factor alone but should be used in combination with established criteria of histological malignancy. It may be especially useful in cases where histology reveals a low-grade astrocytoma whereas other parameters indicate a more malignant neoplasm. Thus, it is our opinion that MIB-1 LI should be a part of the routine investigation in patients with astrocytic tumors. Until larger multicenter studies based on standardized immunohistopathological procedures have been completed, each laboratory has to establish its own practice. (Pathology Oncology Research Vol 12, No 3, 143–147)     

宫颈癌介入化疗前后组织中的CyclinD1、Ki-67的变化及意义

目的:研究宫颈癌术前介入化疗前后组织中的细胞周期蛋白CyclinD1、Ki-67的表达变化及临床意义.方法:采用免疫组化法检测44例处于不同临床分期宫颈癌患者介入化疗前宫颈活检组织以及介入化疗后手术切除标本,观察上述两种蛋白在介入化疗前后的变化情况.结果:介入化疗后CyclinD1、Ki-67呈现不同程度的下降.结论:宫颈癌术前介入化疗可以通过抑制肿瘤细胞的增殖达到抑制肿瘤生长、缩小肿瘤体积进而抑制亚临床转移.     

巢蛋白和Ki-67在恶性外周神经鞘膜瘤中的表达及其意义

 目的　探讨恶性外周神经鞘膜瘤（MPNST）中巢蛋白和细胞增殖核抗原Ki-67的表达情况及其意义。方法　采用免疫组织化学SP法检测42例MPNST中巢蛋白和Ki-67的蛋白表达。24例外周神经良性肿瘤作为对照。结果　MPNST中巢蛋白阳性表达率为95.2 %（40／42）,其中巢蛋白强阳性表达率为40.5 %（17／42）,明显高于外周神经良性肿瘤的4.2 %（1／24）,差异有统计学意义（χ2＝8.403,P＝0.004）;MPNST中Ki-67标记指数介于1 %～70 %之间,其中＞3 %的占64.3 %（27／42）,24例外周神经良性肿瘤中Ki-67标记指数均＜3 %,两者比较差异有统计学意义（χ2＝23.518,P＝0.000）。结论　联合检测巢蛋白和Ki-67免疫标志物有助于MPNST的诊断。     

Intratumoral heterogeneity of MIB-1 labelling index in gastric gastrointestinal stromal tumor (GIST)

Background The MIB-1 labelling index (LI) is used as a prognostic indicator for gastrointestinal stromal tumors (GISTs). However, whether a biopsy-based LI represents the entire tumor is uncertain, because the LI is not always homogeneous. In this study, we examined the extent and characteristics of LI heterogeneity in gastric GISTs. Methods We analyzed ten c-kit-positive gastric GISTs with diameters exceeding 3 cm, of which six were multilobular and four were unilobular. For MIB-1-immunostained sections, continuous digital images were obtained through the maximum diameter of the lobules. We obtained LIs for images by carrying out computer-assisted image analysis, and calculated the means and standard deviations (SDs) of the LIs for the lobules. For each lobule, intralobular heterogeneity was evaluated on the basis of the SD. For multilobular tumors, interlobular heterogeneity was assessed on the basis of the mean LI difference between lobules. Results The SDs, which ranged from 0.8% to 9.8%, indicated intralobular heterogeneity. Moreover, considerable interlobular heterogeneity was noted in five (83%) of the six multilobular GISTs, in which the maximum interlobular mean LI difference ranged from 9.6% to 27.2%. Notably, although the high maximum mean LI (14.1%–32.3%) showed that these five GISTs were high-grade tumors, they also contained at least one lobule showing a low-grade mean LI value (2.7%–5.1%). Conclusion Gastric GISTs often show intralobular or interlobular MIB-1 LI heterogeneity. In multilobular GISTs, multiple biopsy samples may be required for the accurate evaluation of tumor grade.     

Ki-67/MIB-1 as a Prognostic Marker in Cervical Cancer - a Systematic Review with Meta-Analysis

Background: In cervical cancer patients it has been reported that there in a significant Ki-67/MIB-1 expressionis correlated with survival in cervical cancer patients. However, the prognostic value is still not well understood.Materials and Methods: In the present meta-analysis the prognostic value of Ki-67/MIB-1 with regard to overallsurvival (OS) and disease-free survival (DFS) in cervical cancer was investigated. The databases of PubMed, ISIWeb of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct and Wiley OnlineLibrary were used to identify appropriate literature. Results: In order to explore the relationship between Ki-67/MIB-1 and cervical cancer, we have included 13 studies covering 894 patients in the current meta-analysis. Theeffect of Ki-67/MIB-1 on OS for pooled random effects HR estimate was 1.63 (95%confidence interval (CI) 1.09-2.45; P<0.05). The pooled HR for DFS was 1.26 (95%CI 0.58-2.73; P>0.05) and the subgroup analysis indicatedKi-67/MIB1 was associated with DFS (HR=3.67, 95%CI 2.65-5.09) in Asians. Conclusions: According to thismeta-analysis, Ki-67/MIB-1 has prognostic value for OS in patients suffering from cervical cancer. For betterevaluation of the prognostic role of Ki-67/MIB-1 on DFS, studies with larger numbers of patients are needed tovalidate present findings in the future.     

胃肠道间质瘤40例Ki-67、PCNA的表达及意义

目的:探讨Ki-67、PCNA的表达与胃肠道间质瘤(GIST)临床病理特征的关系.方法:应用免疫组化SP法检测40例胃肠道间质瘤中Ki-67、PCNA的表达.结果:40例胃肠道间质瘤中Ki-67、PCNA阳性表达率分别为60.0%、65.0%.Ki-67、PCNA表达与GIST的性别、年龄、部位、组织学分型无关,与肿瘤大小、组织学分级有关.Ki-67、PCNA的表达呈正相关.结论:Ki-67、PCNA联合检测可作为判定GIST良恶性、恶性程度、肿瘤分级及预后的重要指标.     

肾母细胞瘤MIB－1(Ki－67增殖指数)和p27kip1表达及与预后的关系

目的:探讨肾母细胞瘤MIB－1 (Ki－67增殖指数)和细胞周期蛋白依赖性激酶抑制剂p27kip1 的表达及与预后的关系.方法:经医院伦理委员会批准,连续纳入2008 年1 月至2013 年8 月在我院就诊的肾母细胞瘤患者样本作为研究对象,观察p27kip1 和MIB－1 阳性表达与患者临床特征的关系.结果:肿瘤组织中...     

Diagnostic Value of Protein Ki67 (MIB-1) in Atypical Pap Smears of Postmenopausal Women

Background: Atrophic epithelium of cervix sampled from postmenopausal women may mimic high-gradecervical intraepithelial neoplasia in Papanicolaou-stained (Pap) smears. Ki-67 (MIB-1) protein presents onproliferating cells, and percentage of cells with positive nuclei provides a reliable tool for rapid evaluation ofthe growth fraction. The aim of this study was to determine the diagnostic value of protein Ki67 staining inatypical pap smears of postmenopausal women. Methods: In a case-control setting, pap smears of 75 womenwith an atypical pap smear (case group) and 75 with normal pap smears (controls) were obtained before andafter estrogen treatment. Afterward, samples were exposed to the monoclonal antibody Ki-67 (MIB-1) and theimmunohistochemically demonstrated Ki-67+ cells were compared. Results: Mean ages of cases and controlswere 60.4±4.5 and 59.9±4.3 years respectively (P=0.50). There was one (2.7%) positive Ki-67 specimen in thecase group, without any positive Ki-67 specimen in the control group (P=0.50). Conclusions: Measurement ofproliferative activity index in Pap smears restrained with MIB1 is a simple, reliable, and cost-effective methodfor excluding negatives. This would imply that it might allow a substantial reduction of diagnostic estrogencourses and subsequent Pap smears in postmenopausal women with atypical findings.     

乳腺癌旁导管内增生性病变中ER、Ki-67的表达及意义

[目的]探讨ER、Ki-67在乳腺癌旁导管内增生性病变中的表达及意义。[方法]采用免疫组化EnVision法对90例乳腺浸润性导管癌（invasive duetal carcinoma，IDC），癌旁乳腺导管内增生性病变（intraductal proliferative lesion，IDPL）进行ER、Ki-67、CK5／6、CK34βE12、p63、SMA染色标记。[结果]ER在正常终末导管小叶单位（terminal duct-lobular unit，TDLU），普通型导管增生（usual ductal hyperplasia，UDH），非典型性导管增生（atypical ductal hyperplasia，ADH），原位导管癌（ductal carcinoma in situ，DCIS）中的阳性细胞数逐渐增加，并从由少量散在到不连续、连续的片状分布逐渐转变，其中ADH组明显高于UDH组（P〈0．01），DCIS组显著高于ADH组（P〈0．05）。Ki-67在平坦型上皮不典型性（flat epithelial atypia，FEA），DCIS中的表达明显高于ADH（P〈0．05），Ki-67的表达在UDH、ADH中无显著性差异。[结论]ER在UDH、ADH、DCIS中的表达逐渐增加，且两两间均有显著性差异，ER的过表达可能是IDPL恶性转化过程中的改变之一：Ki-67的表达在DCIS组中明显高于ADH组中，Ki-67的表达可能是某些乳腺癌发生的早期事件，两者可作为评估IDPL发生IDC的危险性的生物学指标。     

PCNA和Ki-67在涎腺良、恶性多形性腺瘤中的表达及意义

目的:研究涎腺良、恶性多形性腺瘤的临床病理特点,生物学行为及细胞增殖活性,为其临床诊断及预后评估提供依据.方法:对114例涎腺良、恶性多形性腺瘤进行回顾性分析,对其中20例多形性腺瘤、9例多形性腺瘤生长活跃型及9例恶性多形性腺瘤采用SABC和LSAB免疫组化法观察增殖细胞核抗原(PCNA)和增殖细胞核相关抗原(Ki-67)的表达和分布.结果:恶性多形性腺瘤的PCNA及Ki-67表达水平显著高于多形性腺瘤及多形性腺瘤生长活跃型,其PI值较后二者差异有显著性(P<0.01);良性多形性腺瘤的复发组PCNA和Ki-67的表达明显高于原发组,二者之间有显著性差异(P<0.01).结论:PCNA和Ki-67检测在判断多形性腺瘤恶性增殖方面有重要意义,对良性多形性腺瘤复发预测有重要的参考价值.     

乳腺癌组织Survivin表达与细胞增殖的关系

目的:探讨乳腺癌组织中Survivin表达的临床病理学意义及其与癌细胞增殖的关系.方法:应用免疫组织化学SP法检测Survivin、Ki-67蛋白在96例乳腺癌组织中及20例正常乳腺组织的表达,分析Survivin 表达与Ki-67增殖指数及各临床病理因素的关系.结果:Survivin阳性表达乳腺癌的Ki-67增殖指数(35.32±21.28%)明显高于Survivin阴性者(20.42±11.34%),Survivin表达与肿瘤细胞增殖呈正相关(P<0.01);Survivin在乳腺癌组织中的表达率为70.83%(68/96),正常乳腺组织未见Survivin表达;Survivin蛋白的表达与临床分期、淋巴结转移和5年生存率有关(P<0.05),与年龄、是否绝经、肿瘤大小和组织学分级均无关.结论: Survivin不仅参与凋亡的调控,还促进细胞增殖. Survivin蛋白在乳腺癌中表达上调,提示其通过抑制凋亡在乳腺癌发生、发展中起重要作用,过度表达提示预后不良.     

宫颈癌组织中ADAM-19、Ki-67的表达及临床意义

目的研究早期宫颈癌组织中去整合素基质金属蛋白酶-19（a disintegrin and metallopro-teinase,ADAM-19）、癌细胞增殖指数（Ki-67）的表达及临床意义。方法应用免疫组化sP法检测18例正常宫颈上皮（normal cervical epithelium,NCE）、22例宫颈上皮内瘤变（cervical intraepithelialneoplasm,CIN）和82例宫颈早期浸润癌（invasive cervix carsinoma,ICC）组织中ADAM-19和Ki-67的表达情况。结果在宫颈癌中ADAM-19表达于癌细胞浆和或细胞膜;Ki-67表达于细胞核。从正常宫颈上皮（normal cervical epithelium,NCE）到宫颈上皮内瘤变（cervical intraepithelial neoplasm,CIN）再到宫颈浸润癌（invasivecarsinomacervix,ICC）,ADAM-19、Ki-67的阳性表达率逐步升高（P〈0．05）。ADAM-19在宫颈浸润癌中的表达与盆腔淋巴结转移、脉管浸润、间质浸润、国际妇产科联盟（FIGO）分期、组织学分级和Ki-67表达有关（P〈0．05）;但与年龄和组织学类型无明显相关性（P〉0．05）。有盆腔淋巴结转移、脉管浸润、突破深层间质浸润、FIGO分期为Ⅱ期、组织学分级为Ⅲ级及Ki-67高度表达者,其ADAM-19阳性表达率显著高于无盆腔淋巴结转移、无脉管浸润、浸润深度在浅层间质以内、FIGO分期为Ⅰ期、组织学分级未超过Ⅱ级及Ki-67表达在中度以内者（P〈0．05）。结论ADAM-19阳性表达可能在癌细胞增殖和侵袭转移中起重要作用。ADAM-19过度表达者,癌细胞增殖活跃,更易发生侵袭转移,但并非唯一决定因素。检测宫颈癌中ADAM-19表达对进一步了解宫颈癌生物学行为和判断其预后有一定价值。     

热化疗对恶性胸腔积液中肿瘤细胞表达Ｋｉ-６７、ＰＣＮＡ、Ｂｃｌ-２、ｐ５３的影响

目的　研究射频热疗联合胸腔灌注化疗对恶性胸腔积液中肿瘤细胞表达Ｋｉ-６７、ＰＣＮＡ、Ｂｃｌ-２和ｐ５３的影响。方法　８５例确诊为恶性胸腔积液患者随机分为热化疗组和灌注化疗组,采用中心静脉导管胸腔闭式引流,尽可能排尽胸水后,热化疗组４４例,给予顺铂胸腔灌注化疗,然后进行胸腔射频热疗;灌注化疗组４１例,仅予顺铂胸腔灌注化疗。通过免疫组化法检测治疗前和治疗１疗程后胸腔积液中肿瘤细胞Ｋｉ-６７、ＰＣＮＡ、Ｂｃｌ-２和ｐ５３的表达情况。结果　热化疗组治疗后胸腔积液中肿瘤细胞中Ｋｉ-６７和ＰＣＮＡ的表达率均较治疗前下降,两者比较均有统计学意义（Ｐ＜０.０５）;两组治疗后Ｋｉ-６７、ＰＣＮＡ、ｐ５３和Ｂｃｌ-２的表达率比较均无显著差异（Ｐ＞０.０５）。结论　射频热疗能够显著提高化疗抑制恶性胸腔积液中肿瘤细胞增殖和促进肿瘤细胞凋亡的作用。     

Growth fractions in malignant non-Hodgkin's lymphomas (NHL) as determined in situ with the monoclonal antibody Ki-67

The proportion of proliferating cells in malignant non-Hodgkin's lymphomas (NHL) was determined in situ by immunostaining with the monoclonal antibody Ki-67, which reacts with a nuclear antigen that is present only in proliferating cells. A highly significant correlation could be demonstrated between the proportion of Ki-67 positive cells and the classification into high and low-grade NHL according to the Kiel classification. 93.8 per cent of high-grade and 88.5 per cent of low-grade malignancies were correctly allocated to these groups using the percentage of Ki-67 positive cells as discriminant parameter. On the basis of the medians, the degree of proliferation also paralleled the succession of entities within the Kiel classification. Within most of these different entities, however, the ranges of Ki-67 positive cells varied considerably, indicating that the growth fractions within these groups are rather heterogeneous. Thus it might be useful to determine the growth fraction of each individual case of NHL, because this might be of prognostic value.     

Telomerase activity in colorectal carcinoma and its correlation with expression of c-myc

Objective： To study the role of telomerase activity and c-myc in pathogenesis and progression of colorectal carcinoma, and to investigate the possible regulatory mechanism of telomerase activation. Methods： A modified telomeric repeat amplification protocol （TRAP） and immunohistochemical staining was used to detect telomerase activity and the expression of c-myc in tissue samples from colorectal carcinoma, paracarcinomatousl tissues, normal mucosa, and adenomatoid polyp. Results： The positive rates of telomerase activity and c-myc expression were 83.33% and 80.00% in colorectal carcinoma, 13.33% and 23.33% in paracarcinomatousl tissues, 13.33% and 20.00% in normal mucosa, and 10.00% and 45.00% in adenomatoid polyp respectively, they were significantly higher in colorectal carcinoma than in paracarcinomatousl tissues, normal mucosa, and adenomatoid polyp （P〈0.05）. The rates of telomerase activity and c-myc expression were much higher in colorectal carcinoma with lymph nodes metastases than that without lymph nodes metastases. The expression of c-myc was found being significantly higher in the telomerase positive colorectal carcinoma than in the telomerase negative group （P〈0.05）. Conclusion： The activation of telornerase and abnormal expression of c-myc might play an important role in the process of carcinogenesis and progression of colorectal carcinoma. The over-expression of c-myc may be related to telomerase activation and up-regulation in colorectal carcinoma.     

化疗对骨肉瘤细胞Ki-67及p53表达的影响及其临床病理相关性

目的:探讨术前化疗对骨肉瘤肿瘤细胞增殖活性及p53表达的影响.方法: 应用组织芯片技术及免疫组化法检测58例骨肉瘤患者(其中包括25例化疗后患者)标本中Ki-67及p53的表达情况. 结果: Ki-67的表达在化疗后较化疗前明显下降(P<0.05);化疗后p53的表达略有下降,但无统计学意义(P>0.05);化疗后患者的Ki-67及p53表达与患者的性别、发病部位、组织学类型、肿瘤大小、软组织侵袭及化疗反应均无明显相关性.结论: Ki-67可很好反映骨肉瘤细胞的增殖能力,术前化疗能有效抑制肿瘤细胞的增殖能力;术前化疗对p53的阳性表达率几乎无影响.