葡萄糖转运蛋白-1在不同骨肿瘤中的表达

目的研究葡萄糖转运蛋白-1（GLUT-1）在正常骨组织及不同骨肿瘤标本中的表达情况。方法收集我院临床骨肉瘤标本30例，骨巨细胞瘤标本15例，骨样骨瘤标本10例及正常骨组织标本10例，采用免疫组化染色检测GLUT-1的分布。体外培养骨肉瘤细胞系MG63、临床骨肉瘤细胞、临床骨巨细胞瘤细胞及成骨细胞，RT-PCR检测GLUT-1基因的表达。结果免疫组化显示，骨肉瘤标本GLUT-1染色强阳性占总例数的53％；骨巨细胞瘤切片GLUT-1染色，阳性占总例数的60％；骨样骨瘤标本多为阴性，阴性占总例数的80％；正常骨组织中未见GLUT-1阳性表达。骨肉瘤明显高于与其余3组标本（χ^2=1．622，P=0．009；χ^2=34．667，P〈0．001，χ^2=40．000，P〈0．001）。RT-PCR显示，GLUT-1基因表达存在于MG63细胞、临床骨肉瘤细胞及骨巨细胞瘤中，而正常成骨细胞内并无GLUT-1表达。结论骨肿瘤中存在GLUT-1表达，且GLUT—1与骨肿瘤的恶性程度有较密切的关系。GLUT-1有可能作为判断骨肿瘤恶性程度参考指标及骨肿瘤治疗的新靶点。     

p16、p27蛋白在骨巨细胞瘤和骨肉瘤中的表达

目的：探讨抑癌基因p16、p27在骨巨细胞瘤（GCT）和骨肉瘤（OS）中的蛋白表达特点及其在骨肿瘤发生中的意义。方法：应用SABC免疫组织化学方法检测p16、p27蛋白在16例骨肉瘤、46例骨巨细胞瘤（其中JaffeⅠ级18例、Ⅱ级6例、Ⅲ级12例）。中的表达。结果：p16和p27蛋白的阳性表达均定位于骨肉瘤细胞、骨巨细胞瘤的基质细胞的细胞核和细胞质内。在骨巨细胞瘤Ⅰ级、Ⅱ级、Ⅲ级和骨肉瘤中p16蛋白的阳性表达率依次为16．7％、62．5％、66．7％和25％;p27蛋白的阳性表达率依次为11．8％、56．3％、50％和25％。p26和p27蛋白的骨巨细胞瘤I级中的阳性表达率显著地低于Ⅱ级和Ⅲ级（P＜0．05）,p16蛋白在骨肉瘤与骨巨细胞瘤Ⅲ级之间的阳性率差异有显著性意义（P＜0．05）,而p27蛋白在骨肉瘤和骨巨细胞Ⅲ级之间的率差异则不具有显著性意义（P＞0．05）。结论：p16、p17基因在骨巨细胞瘤和骨肉瘤的发生中起重要作用,但其阳性表达率不足以单独作为判断恶性程度和预后的指标。     

TNF—α、M—CSF及IL—1在骨巨细胞瘤中的表达及其意义

目的：探讨细胞因子与骨巨细胞瘤局部溶骨的关系。方法：采用ELISA法、Western blot分析和免疫组化双染检测了10例骨巨细胞瘤、5例骨肉瘤和5例正常人血清中TNF－α、含量和M－CSF、IL－1的表达,结果：骨巨细胞瘤组织TNF－α、含量和M－CSF表达率明显高于骨肉瘤和正常人。TNF－α、由骨巨细胞的部分单核基因细胞和多核巨细胞分泌;而－CSF及IL－1由部分单核基质细胞份泌,多核巨细胞则不表达。结论骨巨细胞瘤中各种细胞份泌不同的细胞因子可能与该肿瘤的局部溶骨过程。     

666例骨肿瘤发病原因的统计分析

作者通过天津医院近10年经病理证实的666树五种常见骨肿瘤（骨肉瘤、软骨肉瘤、骨软骨瘤、骨巨细胞瘤、软骨瘤），按性别、年龄、部位分布结果分析发现，骨肿瘤发病与人体骨干错端骨结构所受压应力异常有一定关系。五种常见骨肿瘤：骨肉瘤163例，软骨肉瘤对例，骨软骨瘤2（）例，软骨癌31例。0无例骨肿瘤，男女之比为骨肉瘤1．7：1，软骨肉瘤1．扣：1，骨软骨瘤1．幻：1，骨巨细胞瘤1．18：1，软骨瘤1．田河。五种骨肿瘤合计为1．56：1。发病以11岁一30岁年龄组最高。于刀岁后随年龄增长发病呈递减趋势。发病部位显示：股骨下端占第一位，股…     

埃兹蛋白在骨巨细胞瘤中的表达及意义

目的：检测埃兹蛋白（Ezrin）在骨巨细胞瘤组织中的表达,探讨其临床意义。方法将本院2008年1月至2013年12月穿刺活检确诊的60例骨巨细胞瘤设为观察组,同期8例良性病变中的反应性新生骨、12例骨样骨瘤及11例骨母细胞瘤的瘤组织作为对照组,用 Western blotting 及实时 PCR 方法检测 Ezrin 蛋白及基因水平。60例骨巨细胞瘤患者接受瘤段切除加假体置换术,术前均接受2个疗程的化疗,观察化疗前后瘤组织线粒体形态的变化以及 Ezrin 蛋白和基因的变化。结果骨巨细胞瘤中Ezrin 蛋白阳性表达主要位于细胞质中,表达阳性率为76.7%,远高于良性病变中反应性新生骨的19.7%、骨样骨瘤的21.2%以及骨母细胞瘤的20.7%,差异有统计学意义（χ2=4.18,P =0.024）,良性病变中的反应性新生骨组、骨样骨瘤及骨母细胞瘤之间的 Ezrin 表达差异并无统计学意义（χ2=6.18, P =0.087）。化疗后骨巨细胞瘤组织中线粒体固缩及液态空泡现象较治疗前减少,Ezrin 蛋白表达减少,基因水平降低[（23.99±1.49）：（20.11±1.11）,t =5.03,P =0.018）]。结论 Ezrin 在骨巨细胞瘤的表达较其他良性骨肿瘤高,可能成为鉴别良恶性骨肿瘤的辅助生物学指标;对 Ezrin 的早期干预可能有助于骨巨细胞瘤的治疗。     

原发骨肿瘤端粒酶活性的检测及临床意义

目的：探讨端粒酶在原发骨肿瘤组织中的活性表达及临床意义。方法：采用TRAP-ELISA法对21例骨肉瘤、11例骨巨细胞瘤、9例软骨肉瘤、3例骨恶性纤维组织细胞瘤、1例脊索瘤、11例骨软骨瘤、5例骨样骨瘤、4例非骨化性纤维瘤、6例孤立性骨囊肿及7例正常骨组织进行端粒酶活性检测。结果：45例原发恶性骨肿瘤中有38例显示端粒酶活性,阳性率为84.4%,26例良性病变组织中只有2例骨软骨瘤具端粒酶活性,7例正常组织端粒酶表达均为阴性。结论：恶性骨肿瘤组织中端粒酶活性明显高于良性病变和正常组织,有可能成为恶性骨肿瘤的一种潜在性生化标志物和鉴别诊断的指标。     

骨骼

BMP-2、OPN、VEGF的表达在骨肉瘤肺转移中的意义,关节置换术后继发恶性肿瘤,5444例原发性恶性骨肿瘤组织病理学统计分析，侵袭性骨肿瘤保肢关节功能重建手术方法探讨，Ⅰ型胶原吡啶交联终肽诊断肿瘤骨转移的价值,肢体骨恶性肿瘤首次诊治失误患者的挽救治疗,股骨近端骨巨细胞瘤的刮除治疗,     

良恶性骨肿瘤p27蛋白表达与DNA含量研究

目的 :探讨良恶性骨肿瘤细胞 p2 7蛋白表达与 DNA含量的关系及意义。方法 :取骨肿瘤新鲜标本 5 2例(骨软骨瘤 10例 ,骨巨细胞瘤 10例 ,骨肉瘤 2 0例 ,其他恶性骨肿瘤 12例 ) ,运用流式细胞术、单克隆抗体技术和定量免疫荧光技术 ,检测瘤细胞 p2 7蛋白表达、S期细胞百分数 (SPF)及 DNA含量 (DI) ,分析三者之间的关系。结果 :5 2例骨肿瘤 p2 7蛋白表达的平均 FI值为 1.37(骨软骨瘤 2 .2 4± 0 . 38,骨巨细胞瘤 1.79± 0 .36 ,骨肉瘤1.0 6± 0 .39,其他恶性骨肿瘤 1.0 1± 0 .45 ) ;p2 7<1.37组 2 5例 ,均为恶性骨肿瘤 ;p2 7<1.37组的 DI、SPF均明显高于 p2 7≥ 1.37组 (P<0 .0 0 1)。结论 :p2 7蛋白表达减少 ,导致细胞周期失调 ,S期细胞增多 ,DNA合成增强 ,细胞过度增生、恶变 ,可能是骨肿瘤发生发展的原因之一。     

PCNA在骨巨细胞瘤的表达及与病理分级和复发的关系

应用免疫组织化学技术，对32便骨巨细胞瘤进行增殖细胞核抗元原（PCNA）的检测分析，探讨PCNA在骨巨细胞瘤的表达分布及与Jaffe病理分级和复发的关系。结果显示，PCNA的阳性反应只在骨巨细胞瘤波形蛋白阳性的单核基质细胞的胞核中出现，而多核巨细胞均无阳性表达；PCNA在骨巨细胞瘤中的增殖指数虽随Jaffe病理分级增高有呈递增趋势，但各级相互之间在交叉重叠现象；PCNA增殖指数低即低度增生的骨巨细胞瘤复发率低，PCNA增殖指数高即中度和重度增生者复发率明显增高。本文结果进一步支持单核基质细胞是骨巨细胞瘤的主要肿瘤细胞成份的观点，并提示PCNA的表达与Jaffe病理分级不完全一致，但PCNA是判断骨巨细胞瘤预后的一个重要参考指标。     

1513例骨肿瘤及肿瘤样病变统计分析

 本文统计分析了骨肿瘤及肿瘤样病变1513例。其中良性骨肿瘤907例,占59.95%;恶性骨肿瘤450例,占29.74%;肿瘤样病变156例,占10.31%。三组病例都好发于11—40岁,男性较女性多见,为2。28:1。好发部位较多见于股骨、胫骨和肱骨,不同病变有不同的好发部位。良性骨肿瘤中以骨软骨瘤最多见,其次为骨巨细胞瘤。恶性骨肿瘤中以骨肉瘤最多见,其余依次为软骨肉瘤、转移癌、尤文氏瘤、骨髓瘤、骨纤维肉瘤、巨细胞瘤、脊索瘤、皮质旁骨肉瘤、网织细胞肉瘤。骨的肿瘤样病变包括嗜伊红性肉芽肿、骨纤维异常增殖症,弧立性骨囊肿和动脉瘤样骨囊肿。     

Immunohistochemical study on overexpression of c-erbB-2 protein in human breast cancer: its correlation with gene amplification and long-term survival of patients

Using a polyclonal antibody monospecific to the c-erbB-2 oncogene product, an immunohistochemical study on the expression of c-erbB-2 protein was performed in formalin-fixed, paraffin-embedded tissue sections from 176 primary breast carcinomas in which amplification of the c-erbB-2 gene had been detected in 28 cases. Expression of the c-erbB-2 protein was detected in 44 cases (25%), being strongly positive in 27 (15%) and weakly positive in 17 (10%). All cases with amplification of c-erbB-2 showed positive staining of its protein. There were only four cases in which c-erbB-2 was strongly expressed without amplification of the gene. In the group showing strongly positive staining, both overall and disease-free survival were significantly poorer than in the remainder of the cases. Using Cox's regression model analysis, overexpression of c-erbB-2 protein was demonstrated to be an effective prognostic factor independent of nodal status or tumor size.     

c-erbB-2 protein expression and clinicopathologic features in colorectal cancer

Previous reports showed that breast and gastric cancers overexpressing c-erbB-2 protein have a greater metastatic potential and worse prognosis than tumors in which this protein is not overexpressed. The present study was undertaken to examine the significance of c-erbB-2 protein expression as a prognostic factor in colorectal cancer. Protein expression was examined immunohistologically in colorectal cancer tissue from 149 patients without distant metastasis, from 38 patients with liver metastasis, and from 18 patients with lung metastasis. The c-erbB-2 protein-positive rate was significantly higher in cases with lymphatic vessel invasion in the primary tumor, but it did not correlate with lymph node metastases. Expression of c-erbB-2 did not correlate with any other histologic feature (histologic type, depth of tumor invasion, venous vessel invasion, or the clinical stage). The positive rate in the primary lesion was significantly higher in cases with liver metastasis than in cases without liver metastasis, the positive rate was significantly higher in the hepatic than in the primary lesions. The expression of c-erbB-2 protein in colorectal cancer tissue correlates closely with liver metastasis but not with lymphatic or lung metastases.     

骨巨细胞瘤mdm2、p185、p21及p53免疫组化研究

[目的]探讨mdm2、p185、p21及p53在骨巨细胞瘤（GCT）的表达及与GCT病理分级和复发的关系。[方法]应用SP免疫组织化学方法检测mdm2、p185、p21及p53在52例GCT中的表达（GCT按Jaffe分级：Ⅰ级15例、Ⅱ级25例、Ⅲ级12例）。[结果]52例GCT中mdm2、p185、p21及p53的阳性表达率分别为34.6%（18/52）,21.2%(11/52),13.5%(7/52)及26.f9%(14/52)。不同病理分级阳性表达均无显著性差异。mdm2、p185、p21、p53在复发和无复发的病例中,阳性表达率分别为61.5%(8/13)、25.6%(10/39);38.5(5/13)、15.4%（6/39）;23.1%(3/13)、10.3%(4/29);46.2%(6/13)、20.5%(8/39)。GCT复发与否之间的mdm2表达有显著性差异（P=0.018),而p185、p21及p53的表达无显著性差异。[结论]mdm2、p185、p21及p53在GCT中的表达与病理分级差异无关,而mdm2的表达与其复发与否有关。     

骨巨细胞瘤组织中端粒酶hTERT基因表达及其意义

目的 探讨骨巨细胞瘤组织中端粒酶hTERT基因的表达及意义.方法 应用原位分子杂交技术,对4l例骨巨细胞瘤组织、17例骨质增生骨组织、11例异位骨化组织和10例正常骨组织中端粒酶hTERT基因进行检测和定位,并运用图像分析系统对hTERT基因表达水平进行研究.结果 端粒酶hTERT基因在骨巨细胞瘤中表达阳性率为41.5%(17/41),表达强度与骨巨细胞瘤的分化程度明显相关(P＜0.05):低分化肿瘤＞中分化肿瘤＞高分化肿瘤,端粒酶hTERT细胞表达水平与肿瘤细胞的分布定位一致.17例骨质增生骨组织、11例异位骨化组织和10例正常骨组织中端粒酶hTERT基因的表达均为阴性.结论 原位分子杂交是检测端粒酶亚单位hTERT的有效方法,在骨巨细胞瘤细胞水平检测端粒酶hTERT基因的定位诊断具有重要意义.在骨巨细胞瘤发展和维持中端粒酶可能起到重要的作用,同时还可能存在端粒酶以外的机制导致肿瘤细胞永生化.     

原发性输尿管癌p53、c-erbB-2和nm23表达与临床病理特征的关系

目的　研究输尿管癌 p5 3、c- erb B- 2、nm2 3基因的不同表达与其临床病理因素的关系。方法　应用免疫组化 S- P法检测 p5 3、c- erb B- 2、nm2 3等基因蛋白在 2 4例原发性输尿管癌中的表达情况 ,并对其结果与临床病理各参数的关系进行分析。结果　正常输尿管上皮三种基因蛋白均呈阴性 ,在输尿管癌中 p5 3、c- erb B- 2、nm2 3的阳性表达率分别为 41.6 % (10 /2 4)、5 4.1% (13/2 4)和 6 6 .7% (16 /2 4)。 p5 3、c- erb B- 2高表达与输尿管癌分化程度低、浸润至浆膜或浆膜外、生存期短等几项临床病理特征相关。nm2 3的表达与输尿管癌病理分级、浸润深度、临床预后无密切关联。结论　 p5 3、c- erb B- 2和 nm2 3基因参与了输尿管癌的发生发展过程 ,p5 3、c- erb B- 2蛋白表达可以作为输尿管癌生物学行为和预后判断的参考指标 ,两指标同时检测预示作用更可靠     

An immunohistologic evaluation of C-erbB-2 gene product in patients with urinary bladder carcinoma.

BACKGROUND. Amplification or overexpression of the c-erbB-2 gene have been reported to correlate with poor patient prognosis in human breast, gastric, and ovarian cancer. Recently, the c-erbB-2 gene product was found to be expressed frequently in the urinary bladder carcinoma. In the current study, the presence of the c-erbB-2 gene product in urinary bladder carcinomas was compared with patient outcome to evaluate whether c-erbB-2 gene product could identify a subset of patients who are destined to have a poor prognosis. METHODS. Immunohistologic study of the c-erbB-2 gene product was done in formaldehyde-fixed paraffin-embedded tissue specimens obtained from 88 transitional cell carcinomas of the human urinary bladder. Eighty-three patients who underwent complete tumor resection by total cystoprostatectomy (30 patients) or by bladder-preserving operations such as transurethral surgery (50 patients) or partial cystectomy (3 patients) entered a follow-up study. The other five patients did not enter the follow-up study because of lost follow-up (2 patients) or distant metastasis at the time of surgery. RESULTS. The c-erbB-2 gene product was expressed in 23 of 88 patients (26%), showing an increase in the expression rate corresponding to the advancement of tumor grade (P < 0.05) and tumor stage (P < 0.2). The 5-year disease-free survival rate was 48.5% for patients with c-erbB-2 negative tumors versus 9.7% for those with c-erbB-2 positive tumors (P < 0.01). The 5-year actuarial survival rate was 65.5% for patients with c-erbB-2 negative tumors versus 41.8% for those with c-erbB-2 positive tumors (P < 0.05). Multivariate analysis using Cox regression model showed that the c-erbB-2 gene product tissue status was a significant prognostic factor independent of grade and stage of the tumor. CONCLUSIONS. The results suggest that the c-erbB-2 gene product could be a tumor marker to identify a malignant subgroup in bladder carcinomas.     

Overexpression of C-erbb-2 protein in endometrial carcinoma is associated with advanced-stage disease

Expression of the c-erbB-2 product (p185(c-erbB-2)) was examined in plasma membrane isolations from 14 uterine endometrial carcinomas and 3 normal endometrial tissues. Overexpression of p185(c-erbB-2) was found in 8 of 9 endometrial carcinomas of stages III and IV and in none of 5 early stage specimens, when compared with the level in normal endometrial tissues. The expression of p185(c-erbB-2) was independent of histological grade. When the p185(c-erbB-2) immunoprecipitated with anti-p185(c-erbB-2) antibodies was exposed to adenosine triphosphate, enhanced self-phosphorylation occurred more frequently in specimens from the tumors carrying p185(c-erbB-2) overexpression. These findings demonstrated positive correlation between disease spread, p185(c-erbB-2) expression and autophosphorylation of p185(c-erbB-2) in human endometrial carcinoma. The prognostic value of these observations awaits continued study.     

p53 、bcl-2 和CD44v6 蛋白表达与乳腺癌转移的相关性研究

 目的 探讨乳腺癌及癌旁正常乳腺组织中p53、bcl—2和CD44v6蛋白的表达及意义。方法 采用免疫组化法检测96例乳腺癌及其癌旁正常乳腺组织中p53、bcl—2和CD44v6蛋白的表达，并分析其与淋巴结转移和c-erbB-2表达状态的相关性，从而评价这些指标在预测乳腺癌转移方面的价值。结果 正常乳腺组织中p53蛋白为阴性，在乳腺癌中阳性表达率为65．63％；随着组织学分级的增高，阳性率逐渐增高；淋巴结转移组阳性表达率明显高于无淋巴结转移组，并与c-erbB-2表达状态呈正相关。乳腺癌组织中bcl-2阳性表达率明显低于周围正常乳腺组织，随着组织学分级的增高，阳性率逐渐降低，淋巴结转移组中的表达率明显低于淋巴结非转移组，与c-erbB-2的表达呈负相关。CD44v6在乳腺癌组织中的阳性表达率明显高于正常乳腺组织，随着组织学分期的增加，CD44v6的阳性表达率亦增高，但差异无显著性，淋巴结转移组的阳性率略高于无淋巴结转移组，差异也无显著性，与c-erbB-2表达无相关性。结论 p53和bcl-2蛋白可作为预测乳腺癌转移的指标，CD44v6的阳性表达可能与乳腺癌的发生、进展有一定关系，但尚不能把它作为预测乳腺癌转移的稳定的生物学指标。     

Clinical and prognostic significance of PD-1 and PD-L1 expression in sarcomas

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are new targets in cancer immunotherapy in recent years. The aim of this study is to evaluate the PD-1/PD-L1 expressions in sarcomas and to determine association between PD-1/PD-L1 expressions and clinical/pathological properties in some sarcoma subtypes. Formalin-fixed, paraffin-embedded tissue samples from 65 cases with sarcomas were analyzed. Immunohistochemical staining was performed to detect the PD-1 and PD-L1 expressions in tumor tissue and microenvironment, separately. PD-1 expression in tumor tissue and microenvironment was detected in 11 (17 %) and 8 (12 %) cases, respectively. PD-L1 expression in tumor tissue and microenvironment was detected in 19 (29 %) and 20 cases (30 %), respectively. None of the 5 Ewing sarcomas involving bone showed PD-1/PD-L1 expression, while 2 of 3 cases with Ewing sarcomas involving soft tissue showed PD-1 and PD-L1 expression. Among 5 cases with Kaposi sarcoma, four showed PD-1 and/or PD-L1 expression in tumor or microenvironment. PD-1/PD-L1 expressions were detected 3 of 6 cases with pleomorphic sarcoma, 2 of 4 cases with peripheral nerve sheath tumors and 1 of 4 cases with synovial sarcoma. Interestingly, strongest PD-1/PD-L1 expressions in our study group were detected in 2 sarcoma cases with the history of giant cell tumor. PD-1 and PD-L1 expressions are up to 30 % of the cases with sarcomas. It may be rational to target programmed death pathway in Kaposi sarcoma, pleomorphic sarcoma and peripheral nerve sheath tumors. Strong expression of PD-1/PD-L1 in cases with previous giant cell bone tumor has been found to be interesting and must be studied in giant cell tumor samples.