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.     

Ki-67抗原在原发性胆囊癌中的表达及其意义

目的探讨Ki-67抗原表达与原发性胆囊癌病理生物学行为的关系.方法采用免疫组化S-P法,检测胆囊良、恶性病变中Ki-67抗原的表达情况,以其表达阳性率评估胆囊癌组织的增生活性.结果Ki-67抗原在胆囊癌组织中的表达量显著高于胆囊良性病变(P＜0.01).但Ki-67抗原的表达强度与胆囊癌组织学类型、Nevin分期及病理分级无明显相关性(P＞0.05),与胆囊癌的突变型p53基因产物表达量呈明显正相关(P＜0.05).结论Ki-67抗原作为1个代表增殖活性的肿瘤标志,其过量表达是胆囊癌高度恶性的生物学行为的客观指标之一,对胆囊恶性肿瘤的病理诊断有较高的实用价值.p53基因可能通过基因突变增强胆囊癌细胞的增殖活性,从而使Ki-67抗原表达量明显增加.     

Ki-67抗原在膀胱癌中的表达及其意义

目的探讨Ki-67抗原在膀胱癌中的表达及其与膀胱癌分级、分期的关系。方法采用免疫组织化学法检测Ki-67抗原在60例膀胱癌患者和20例膀胱良性病变和10例正常膀胱黏膜中的表达。结果Ki-67抗原在60例膀胱癌标记指数为25．9％,在20例膀胱良性病变为103％,在10例正常膀胱黏膜中为1．1％,各组间差异有统计学意义;Ki-67抗原随着膀胱癌病理分级和临床分期的增加而表达升高。结论Ki-67抗原在膀胱癌细胞中表达升高并与膀胱癌分期、分级密切有关,Ki-67的表达可以作为评价细胞增生状态的指标,有可能成为判断肿瘤发生、发展、预后的重要指标。     

Ki-67、CDK4表达与中晚期乳腺癌新辅助化疗效果的相关性分析北大核心

目的:分析Ki-67核抗原(Ki-67)、CDK4表达与中晚期乳腺癌新辅助化疗(NACT)效果的相关性。方法:回顾性选取2016年4月至2018年6月我院的中晚期乳腺癌患者70例,均于新辅助化疗后实施手术,依据化疗效果分为有效组、无效组,采用免疫组化法检测两组化疗前Ki-67、CDK4表达水平,比较不同Ki-67、CDK4表达水平患者病理完全缓解率(pCR)、2年复发转移情况。结果:有效组Ki-67高表达率、CDK4阳性率高于无效组(P<0.05);Ki-67高表达患者pCR率高于Ki-67低表达者,CDK4高表达者pCR率高于CDK4低表达者(P<0.05);Kaplan-Meier曲线显示,Ki-67低表达的乳腺癌患者2年复发转移率低于Ki-67高表达者(P<0.05),CDK4高表达的乳腺癌患者2年复发转移率与CDK4低表达者无明显差异(P>0.05);Spearman相关分析显示,乳腺癌患者Ki-67、CDK4表达变化与化疗效果呈正相关(r=0.569、0.481,P<0.05)。结论:Ki-67、CDK4高表达的乳腺癌患者经NACT后获得pCR率更高,化疗疗效更优,但Ki-67高表达者预后较差,CDK4表达情况与预后相关性不大。     

MGMT和Ki-67抗原在肝细胞癌组织中的表达及意义

目的 探讨O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)和细胞增殖核抗原Ki-67在原发性肝细胞肝癌(HCC)组织中的表达及意义.方法 应用免疫组化S-P法检测68例HCC组织及癌旁组织中MGMT及Ki-67抗原的表达.结果 MGMT、Ki-67抗原在HCc组织中的表达率分别为44.12%(30/68)和57.35%(39/68),MGMT的表达与Hcc组织病理分级有关(P<0.05),与其它临床因素无关(P>0.05);Ki-67抗原的表达与HCC的肿瘤大小、包膜是否完整、脉管有无癌栓、病理分级有关(P<0.05),与血清AFP的浓度无关(P>0.05);并且随Ki-67抗原表达强度的增加,MGMT的表达强度明显下降,Ki-67抗原与MGMT表达呈负相关(γ=-0.301,P<0.05).结论 MGMT在HCC的发生发展中可能起抑制作用,MGMT的缺失是HCC发生的重要分子事件之一,检测Ki-67抗原有助于判断HCC恶性程度及复发转移的风险,联合检测MGMT和Ki-67抗原有助于预测HCC患者预后.     

人脑胶质母细胞瘤Ki-67抗原表达及其预后作用

目的探讨Ki-67抗原在人脑胶质母细胞瘤中的表达及其预后作用.方法使用S-P免疫组化方法检测31例人脑胶质母细胞瘤标本中Ki-67抗原的表达.单因素使用Kaplan-Meier法,多因素分析使用COX比例风险模型进行预后分析.结果Ki-67LI为(8.07±3.84)%.单因素及多因素分析均显示Ki-67指数是独立的预后因素.Ki-67指数≤2.5%与＞2.5%的患者生存期分别为(46.17±17.21)月、(12.43±5.01)月,P＜0.01.结论在人脑胶质母细胞瘤中,Ki-67指数不同,其预后也有显著不同.Ki-67指数＞2.5%提示预后较差.     

大肠良、恶性肿瘤Ki-67抗原的表达及其意义

目的研究细胞增殖相关的核抗原(Ki-67抗原)在正常大肠粘膜以及大肠良、恶性肿瘤中的表达,探讨其临床意义.方法收集33例大肠癌、13例大肠良性肿瘤和13例正常粘膜的手术标本,用流式细胞术检测Ki-67抗原表达.结果大肠正常粘膜以及良、恶性肿瘤的Ki-67抗原标记指数(Ki-67抗原阳性细胞比例)分别为2.65%±1.51%、6.38%±2.51%、18.52%±8.53%,组间两两比较均存在显著性差异(P＜0.05);流式细胞仪检测Ki-67抗原表达鉴别大肠良、恶性肿瘤的灵敏度、特异性分别为75.76%和69.23%,Ki-67抗原表达在大肠癌的病理类型、Dukes分期、肿瘤体积、部位、病程、年龄、性别的组间两两比较,差异均没有显著性(P＞0.05).结论流式细胞仪检测Ki-67抗原表达是大肠正常粘膜以及良、恶性肿瘤间相鉴别的一项有价值的指标.     

软组织肉瘤Ki-67和EGFR及PDGFR表达与预后相关性分析

目的:探讨软组织肉瘤中增殖细胞核抗原Ki-67、EGFR和PDGFR表达状况对判断预后的临床价值.方法:免疫组化法检测60例软组织肉瘤患者瘤体组织Ki-67、EGFR和PDGFR的表达水平,结合短期随访观察Ki-67EGFR和PDGFR不同表达的患者总生存率和复发率的差异.结果:Ki-67阴性表达患者第1年和第2年总生存率分别为100.0％和95.5％,均高于阳性表达患者的83.9％和76.0％;Ki-67阴性表达患者第1年和第2年复发率分别为6.9％和8.3％,高于阳性表达患者的22.6％和48.0％.EGFR与Ki-67均为阳性表达与均为阴性表达的患者,第1、2年的总生存率差异无统计学意义,P＞0.05;PDGFR与Ki-67均为阳性表达与均为阴性表达的患者,第1、2年的总生存率差异无统计学意义,P＞0 05.结论:增殖细胞核抗原Ki-67在软组织肉瘤中阳性表达提示预后不良,增加EGFR、PDGFR与Ki-67进行双指标检测并未提高预测的敏感性.     

Ki-67表达与Ⅱ/Ⅲ期乳腺癌新辅助化疗疗效及预后的关系

目的:探讨乳腺癌组织中Ki-67 抗原（简称 Ki-67）表达与新辅助化疗(neoadjuvant chemotherapy,NAC)疗效的关系。寻找新辅助化疗有效的预测因子。方法:选取我院2012年6月至2017年6月收治的112例接受NAC治疗的Ⅱ/Ⅲ期乳腺癌患者作为研究对象。使用免疫组化方法检测NAC治疗前乳腺癌患者的Ki-67表达情况，化疗2~4周期后评估临床疗效。分析乳腺癌中Ki-67的表达与临床病理学特征的关系以及Ki-67的表达与NAC疗效的关系。结果:原发性乳腺癌组织中Ki-67的高表达率为65.18%，Ki-67的高表达与病理组织学分级（P=0.017）有关。Ki-67高表达的患者新辅助化疗后获得临床完全缓解（cCR）+临床部分缓解（cPR）的比率（89.0%）明显高于Ki-67低表达的患者新辅助化疗后获得cCR+cPR的比率（61.5%）（P=0.001）。中位随访时间 37个月，Ki-67高表达患者的无病生存时间（DFS）低于Ki-67低表达的患者（P=0.023），Ki-67高表达患者的总生存时间（OS）低于Ki-67低表达的患者（P=0.040）。结论:Ki-67的高表达与乳腺癌恶性程度密切相关，并可作为预测乳腺癌新辅助化疗敏感度及预后的独立指标。     

喉癌Ki-67抗原表达的初步研究

目的观察Ki-67抗原在喉癌的表达及与转移、预后的关系.方法用SP免疫组化法测定45例喉癌手术标本蜡块的常现病理切片中Ki-67抗原的表达,并取9例正常喉粘膜组织和7例喉良性病变作对照.结果 Ki-67抗原在喉癌组织的表达远高于正常喉粘膜组织、喉良性病变中的表达,有明显差异(P＜0.05;P＜0.05).在有临床转移者与无临床转移者之间及死亡与未死亡病例间未见明显差异(P＞0.25;P＞0.25).结论 Ki-67抗原表达的阳性率对诊断喉部病变的性质有较高的实用价值,但尚不能判断喉癌的转移和预后.     

肛管直肠恶性黑色素瘤的临床病理特征分析

目的探讨肛管直肠恶性黑色素瘤（anorectal malignant melanoma,AMM）的临床病理学特征。方法收集南京中医药大学附属南京中医院2008年7月至2019年8月收治的15例AMM患者的临床病理资料,分析其临床及病理组织学特征、免疫表型及BRAF基因突变情况,并复习相关文献进行分析。结果15例AMM患者年龄45～88岁（中位年龄66岁）,男5例,女10例。临床主要表现为便血、肛管直肠肿物、肛门坠胀疼痛。15例中仅有2例临床诊断为恶性黑色素瘤。镜下肿瘤细胞形态多样,异型性明显,核大,核仁明显,胞浆内可见黑色素颗粒。免疫组化结果显示肿瘤细胞表达S 100、Vimentin、HMB 45及Melan A,不表达CK、EMA、LCA,Ki 67表达10%～60%阳性不等,1例可见BRAF基因突变。结论AMM是一种临床少见、预后较差的恶性肿瘤,临床表现无特异性,临床误诊率高,明确诊断需结合免疫组化标记物检查。治疗上以手术为主,辅以放疗、化疗及免疫治疗等。     

High homogeneity of MAGE,BAGE, GAGE,Tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simultaneous metastases of human melanoma: Implications for protocol design of therapeutic antigen-specific vaccination strategies

Human melanoma cells express several antigens which are recognized by autologous and specific CTL clones in association with HLA-class-I molecules. Many of these antigens represent suitable targets for tumor immunotherapy, since their expression in human melanoma cells is common and highly specific. In order to achieve real clinical success with therapeutic vaccination strategies, one important requirement is the expression of the target antigen by all the tumor lesions of a patient. We have studied this issue by assessing, through an RT-PCR approach, the expression of MAGE-1, MAGE-2, MAGE-3, BAGE, GAGE-1/2, Tyrosinase and Melan-A/MART-1 genes in 17 clusters of simultaneous in-transit or regional lymph-node metastases collected from 15 stage-III and 1 stage-IV (AJCC/UICC pTNM system) melanoma patients. In 14 out of 17 clusters of simultaneous metastatic lesions (82%), the homogeneity in the pattern of gene expression within the cluster was complete. Heterogeneity within the same cluster was observed in only 3 out of 17 clusters (18%) and represented only minor features. Our data reveal that, in AJCC-stage-III melanoma patients, different but simultaneous metastatic lesions express the same pattern of antigen-coding genes. These observations have 2 main clinical implications: (i) the antigenic characterization of one single and easily accessible lesion allows identification of optimal targets for an active antigen-specific immunotherapy treatment; (ii) almost all the metastatic lesions are expected to be hit by the immune response eventually induced against the tumor antigen. Moreover, these data suggest that active specific immunotherapy directed against MAGE-1, MAGE-3, BAGE, GAGE-1/2, Melan-A/MART-1 and Tyrosinase antigens could be exploited as an adjuvant treatment to surgery in high-risk AJCC-stage-III-melanoma patients. Int. J. Cancer 77:200–204, 1998.© 1998 Wiley-Liss, Inc.     

可溶性PD-L1作为晚期肢端及黏膜黑色素瘤预后因素的研究

目的:可溶性PD-L1(sPD-L1)水平升高与肾细胞癌和多发性骨髓瘤预后相关.然而,sPD-L1在晚期黑色素瘤中的调节作用和功能尚不完全清楚.本研究旨在评估晚期肢端及黏膜黑色素瘤患者循环系统中sPD-L1浓度与预后的关系.方法:于2012年1月至2015年12月期间在北京大学肿瘤医院招募了未经治疗的晚期肢端及黏膜黑色...     

黏膜无色素性恶性黑色素瘤的免疫组化及临床研究

 目的 探讨CD56，CD95（Fas），Ki-67，p53，bcl-2，HMB45和S-100在恶性黑色素瘤（恶黑）中的表达，以提高黏膜无色素性恶黑的病理诊断准确率，减少误诊和漏诊，并为临床估计预后、选择治疗方案提供客观指标。方法 应用组织芯片和免疫组化标记技术，对48例黏膜无色素性恶黑进行标记和分析。结果 HMB45与S-100的阳性率分别是100 %和85.4 %（41／48）。CD56的阳性率为91.6 %（44／48），在转移灶与原发灶中差异无统计学意义（P＞0.05）。CD95的阳性率为85.4 %（41／48），其中在11例有淋巴结转移的病例中，阳性率达100 %。Ki-67与p53阳性率分别为79.2 %（38／48）和58.3 %（28／48），Ki-67的阳性分布与CD95基本一致。bcl-2的阳性率为39.6 %（19／48）。p53和bcl-2在恶黑中的表达阳性率与CD95比较差异具有统计学意义（P＜0.05）。结论 CD56在恶黑中具有重要的辅助诊断价值；CD95（Fas）与Ki-67的表达对判断恶黑浸润范围及淋巴结转移状况和指导临床治疗有一定的意义。     

Amelanotic Anorectal Malignant Melanoma: Case Report with Immunohistochemical Study and Literature Review

Epithelioid cell tumors presenting in the gastrointestinal tract are uncommon, but when they arise, arriving at a correct diagnosis is important. We report a case of anal malignant melanoma in an 82-year-old man who microscopically showed an epithelioid malignant tumor simulating a gastrointestinal stromal tumor. C-kit stain and Melan-A were diffusely and strongly positive, while HMB-45 was focally positive. This case illustrates the potential pitfall of relying on a single antibody or inadequate panel of immunohistochemical stains to confirm the diagnosis. We recommend to apply an adequate immunohistochemical panel which includes S-100 protein, HMB-45 and Melan-A in order to make an accurate diagnosis, and discuss the differential diagnosis and surgical treatment modalities.Key Words: Malignant melanoma, Rectum, Anus, Immunohistochemistry, Gastrointestinal stromal tumor     

Angiomyolipoma of the kidney: Clinicopathological and immunohistochemical study

OverviewAlthough angiomyolipoma (AML) is a relatively rare entity, it is the most common benign mesenchymal neoplasm of the kidney.The aim of this studyTo highlight the clinicopathological characteristics of AML and to assess the role of Human Melanoma Black-45 (HMB-45), Melan-A, smooth muscle actin (SMA), S-100 and cytokeratin in its diagnosis.Materials and methodsThe study included 15 cases of AML. Clinical and radiological data were retrieved from the archival files and all cases were subjected to a histopathological evaluation as well as immunohistochemical staining for HMB-45, Melan-A, SMA, S-100, and cytokeratin.ResultsAML was more common in females (female:male = 4:1), the mean age was 53.9 ± 6.45 years. 60% of patients were symptomatic while the remaining 40% were asymptomatic. A statistically significant relationship was found between size of the tumor and the presence of the symptoms (P = 0.02). Patients with tumor size less than 4 cm were asymptomatic, while those with tumor size larger than 4 cm had different symptoms.Thirteen cases were classic AML, while 2 cases were epithelioid AML. Classic AML demonstrated admixture of fatty tissue, thick-walled blood vessels, and smooth muscle, while epithelioid AML was composed mainly of epithelioid cells and contained no fat. HMB-45 was positive in all cases of AML (100%), Melan-A was positive in 13/15 (87%) while SMA was positive in 11/15 (73%) of AML with variable staining intensity. All cases of AML were negative for S-100 and cytokeratin.ConclusionAMLs have characteristic clinicopathological and immunohistochemical features and their recognition is crucial for proper diagnosis and treatment.     

Concordant loss of melanoma differentiation antigens in synchronous and asynchronous melanoma metastases: implications for immunotherapy

Because of its known heterogeneity, the analysis of antigen expression is crucial prior to the initiation of antigen-specific immunotherapy for melanoma. The melanoma differentiation antigens gp100, MART-1 and tyrosinase are involved in a common pathway of melanin synthesis. Peptides derived from these melanoma differentiation antigens are used in the immunotherapy of melanoma and antibodies recognizing these antigens are commonly applied to detect melanocytic lesions. One hundred and ninety-one paraffin-embedded melanoma metastases from 28 patients with 2-19 lesions (mean, 6.8) developing synchronously (n = 67) or asynchronously (n = 124) were analysed by immunohistochemistry for the expression of the melanoma differentiation antigens, as well as cancer/testis antigens of the melanoma antigen-A (MAGE-A) family (monoclonal antibodies 77B and 57B), anti-S100 and SM5-1. The overall reactivities were 81.6% (gp100), 79.5% (MART-1), 59.6% (tyrosinase), 59.1% (77B), 60.7% (57B), 93.2% (S100) and 91.6% (SM5-1). Twenty-seven lesions (14.1%) were positive for all tumour-associated antigens, 75 lesions (39.2%) were negative for one antigen and 87 lesions (45.5%) were negative for several tumour-associated antigens. Co-ordinated loss was found for lesions negative for gp100 and MART-1 (9.4%, P < 0.0005), gp100 and tyrosinase (11.0%, P = 0.009), MART-1 and tyrosinase (15.2%, P < 0.0005) and gp100, MART-1 and tyrosinase (8.9%, P < 0.0005), which is up to six times higher than the expected calculated loss. This co-ordinated loss of melanoma differentiation antigens in melanoma did not include cancer testis antigens and S100 or SM5-1. On average, the melanoma differentiation antigens stained 50-65% of cells within a lesion, and 10-39% of synchronous clusters were heterogeneous for melanoma differentiation antigen expression. In conclusion, broader polypeptide vaccines should be used for melanoma immunotherapy.     

Prognostic evaluation of cutaneous malignant melanoma: a clinicopathologic and immunohistochemical study

BACKGROUND AND OBJECTIVES: Depth of invasion and stage of the disease are established prognostic indicators in cutaneous malignant melanoma. The role of other parameters is still an open problem. METHODS: In 93 consecutive patients with cutaneous malignant melanoma, the level of invasion, tumor thickness, ulceration, vascular invasion, lymphoplasmocytic infiltrates, and mitotic index were evaluated by histology. Expression of Ki-67 and PCNA proliferative antigens together with vimentin, S100, and HMB 45 proteins were assessed by immunohistochemistry. RESULTS AND CONCLUSIONS: Disease-free and overall survival were correlated with tumor stage, tumor thickness, level of invasion, macroscopic pattern, ulceration, vascular invasion, expression of HMB 45, PCNA, and Ki-67/MIB1. Stage, HMB 45, and PCNA were independent prognostic factors for disease-free survival, whereas tumor stage, tumor thickness, and expression of both proliferative antigens influenced overall survival independently. The variables studied demonstrated reciprocal correlation; therefore, analysis of many prognostic parameters in malignant melanoma could be recommended.