Expression of nm23-H1 and nm23-H2 protein in endometrial carcinoma.

nm23 gene expression has been shown to be inversely correlated with tumour metastatic potential in some cancers but not in others. Examination was made of the expression of nm23-H1 and nm23-H2 gene products by immunohistochemistry and immunoblotting in 28 endometrial carcinomas. Immunohistochemistry indicated the cytoplasm of cancer cells to be positive, and myometrium and endometrial stromal cells negative, for nm23-H1 and -H2 protein. The staining intensity for these proteins was significantly stronger in well-differentiated adenocarcinomas (G1) than in those moderately differentiated (G2) (P < 0.05). nm23-H1 and -H2 proteins were shown by immunoblotting to be present at significantly higher levels in G1 than in G2 tumours (P < 0.05). Two of eight cases expressed high nm23-H1 and -H2 protein in poorly differentiated adenocarcinomas (G3). In G3 tumours, nm23 expression may be diverse. In this study, the expression of nm23-H1 and -H2 was not correlated with stage, metastasis, tumour size, myometrial invasion, oestrogen receptor, progesterone receptor or menopause. It follows from the findings presented above that the high expression of nm23-H1 and -H2 is positively correlated with histological differentiation.     

nm23-H1与大肠癌微转移关系的研究

目的探讨nm23-H1基因表达与大肠癌浸润、微转移和预后的关系。方法经病理确诊的120例大肠癌组织标本,采用SP法检测nm23-H1基因蛋白表达、巢式RT-PCR方法检测进入外周静脉血的大肠癌微转移灶(CK20mRNA),并与同一患者大肠癌组织标本中nm23-H1基因表达情况进行综合分析。结果nm23-H1在大肠癌中的阳性表达率为61.7%(74/120),低分化腺癌中nm23-H1阳性表达率(41.0%)显著低于高中分化腺癌中的表达率(70.3%)(P<0.05);有淋巴结转移者nm23-H1阳性表达率为53.7%,无淋巴结转移者为71.7%,两组比较有显著性差异(P<0.05);120例大肠癌患者术后3年随访中,CK20mRNA阳性检出率为41.5%,nm23-H1阳性表达率与CK2OmRNA阳性率呈显著负相关(P<0.001);nm23-H1蛋白阳性表达组术后3年生存率为60.8%(45/74),阴性表达组术后3年生存率为21.7%(10/46),二组比较有显著性差异(P<0.001)。结论nm23-H1与大肠癌细胞分化、淋巴结转移及外周静脉血中微转移密切相关,是影响大肠癌预后的重要指标之一。     

Expression of nm23-Hl and nm23-H2 Proteins in Prostate Carcinoma

The nm 23 gene products/nucleoside diphosphate (NDP) kinase expression in prostate carcinomas and benign hyperplasias was evaluated immunohistochemically. Monoclonal antibodies against nm 23-H1 and nm 23-H2 proteins were prepared using the corresponding proteins fused with glutathione S-transferase as immunogens. Of the 80 cases of nonmetastatic prostate carcinoma examined, 74% (59/80) and 60% (48/80) were immunoreactive for nm 23-H1 or nm 23-H2 protein, respectively. Negative staining for nm 23-H1 occurred in 83% of metastatic lesions, while 34% were negative for nm 23-H2. All primary tumors corresponding to the metastases examined showed positive immunostaining for nm 23-H1, indicating an inverse relationship between expression of this protein and metastatic status. nm 23-H2 protein was detected in 83% of primary tumors and its expression appeared to he significantly correlated to the degree of histological differentiation. In contrast, all cases of benign prostatic hyperplasia showed elevated levels of both nm 23-H1 and nm 23-H2 expression. These data suggest that the nm 23/NDP kinase may play a role in suppressing the expression of malignant potential in prostate carcinomas.     

膀胱癌中nm23-H1基因突变及表达的意义

目的：探讨ｎｍ２３－Ｈ１基因在膀胱癌中突变及表达的意义。方法：应用半定量逆转录聚合酶链反应（ＲＴ－ＰＣＲ）和银染单链构象多态性（ＳＳＣＰ）方法检测ｎｍ２３－Ｈ１基因在２５例膀胱癌组织及１５例对照组织中突变和表达情况。结果：对照粘膜中未检测出ｎｍ２３－Ｈ１基因突变,而在２５例膀胱癌组织中发现６例出现ＰＣＲ产物单链泳动状态异常,异常率为２４％。癌组织和对照组织均有ｎｍ２３－Ｈ１基因ｍＲＮＡ的表达,８８     

垂体腺瘤nm23-H_1基因表达的临床意义

目的明确nm23-H_1基因在垂体腺瘤中的表达及其临床意义。方法采用免疫组织化学染色（SP）法对62例垂体腺瘤nm23-H_1基因表达进行回顾性研究。结果侵袭型垂体腺瘤nm-H_1基因表达水平显著低于非侵袭型（P＜0.01）;Ⅲ、Ⅳ级垂体腺癌nm23-H_1基因表达水平显著低于Ⅰ、Ⅱ级（P＜0.05）;nm23-H_1基因表达水平下降与垂体腺瘤患者的性别、年龄及肿瘤分泌功能无显著相关性（P＞0.05）。结论nm23-H_1基因可能在会作腺瘤的侵袭过程中起重要作用,其表达改变是反映垂体腺癌侵袭性的敏感指标。     

E-cadherin及nm23-H1在滋养细胞疾病中的表达及意义

目的:探讨E-cadherin及nm23-H1基因在妊娠滋养细胞疾病发生发展中的作用.方法:采用免疫组化法检测24例葡萄胎(随访2年以上未发生恶变)、15例侵蚀性葡萄胎、15例绒毛膜上皮癌、18例正常绒毛组织的石蜡包埋标本E-cadherin和nm23-H1基因的表达状况.结果:E-cadherin的表达在正常早孕绒毛高于侵蚀性葡萄胎和绒毛膜癌(P＜0.01),葡萄胎高于侵蚀性葡萄胎和绒毛膜癌(P＜0.05).nm23-H1的表达正常早孕绒毛明显高于恶性滋养细胞疾病(P＜0.01),葡萄胎高于侵蚀性葡萄胎(P＜0.01)和绒毛膜癌(P＜0.05).在葡萄胎和恶性滋养细胞疾病中E-cadherin和nm23-H1基因的表达均为正相关.结论:滋养细胞疾病E-cadherin和nm23-H1表达与其侵袭性相关,二者可能成为葡萄胎预后的标志物.在侵袭转移过程中细胞滋养细胞较合体滋养细胞更为重要.     

nm23-H1与Tiam1在睑板腺癌中的表达及意义

目的:检测睑板腺癌组织中nm23-H1及Tiam1的表达,探讨其与临床病理特征的关系,评价其临床意义.方法:睑板腺癌标本34例及癌旁正常组织34例,应用Western blot法及qRT-PCR检测nm23-H1和Tiam1蛋白及mRNA的表达,观察其蛋白水平表达与临床病理特征的相关性,观察其与睑板腺癌术后复发的关系.结果:nm23-H1蛋白及mRNA在睑板腺癌组织中表达高于癌旁组织(P<0.05),Tiam1蛋白及mRNA在睑板腺癌组织中表达高于癌旁组织,差异有统计学意义(P<0.05).nm23-H1 及Tiam1蛋白表达水平与肿瘤直径、TNM分期、淋巴结转移及肿瘤分化程度有相关性(P<0.05),nm23-H1 及Tiam1与睑板腺癌术后复发率具有相关性,在复发的睑板腺癌中nm23-H1及 Tiam1表达高于未复发者(P<0.05).结论:nm23-H1和Tiam1表达水平与睑板腺癌的临床病理特征具有相关性,nm23-H1和Tiam1高表达提示睑板腺癌患者不良预后.     

肿瘤转移相关基因在甲状腺乳头状癌的表达与颈淋巴结转移相关性研究

目的：探讨肿瘤转移抑制相关基因nm23-H1,转移相关基因CD44v6在甲状腺乳头状癌的表达与颈淋巴结转移的关系。方法：采用免疫组化S－P法,检测201例甲状腺乳头状癌、30例甲状腺良性病变及30例正常甲状腺组织中nm23-H1和CD44v6的表达情况。结果：1）nm23-H1在甲状腺乳头状癌组的表达阳性率62．7％,明显低于良性病变组和正常组（P＜）．01或P＜0．05）。有转移组nm23-H1的阳性率为54．5％,明显低于无转移组（75．0％）,其蛋白表达与颈淋巴结转移呈负相关。2）CD44 v6在甲状腺乳头状癌组的表达阳性率为71．1％,明显高于两对照组（P均＜0．01）。有转移组CD44v6的阳性率为79．3％,明显高于无转移组（58．5％）,其蛋白表达与颈淋巴结转移呈正相关。3）甲状腺乳头状癌中nm23-H1和CD44v6表达呈显著负相关关系（P＜0．01）。nm23-H1阴性表达伴CD44v6阳性表达的患者发生颈淋巴结转移的可能性大。结论：nm23-H1和CD44v6的表达与甲状腺乳头状癌的颈淋巴结转移密切相关,nm23-H1和CD44v6的表达在淋巴结转移中起协同作用,两者的表达失衡可能与甲状腺乳头状癌发生颈淋巴结转移有密切关系。因此,检测nm23-H1和CD44v6可能作为预测甲状腺乳头状癌颈淋巴结转移潜能的有价值的参考指标。     

非黑素性皮肤癌中nm23-H1的表达和意义

目的　探讨nm2 3 H1在非黑素性皮肤癌的表达和意义。方法　用单克隆抗体免疫组织化学S P法检测在非黑素性皮肤癌 46例 ,nm2 3 H1阳性细胞数 >3 0 %的癌细胞为过度表达。结果　正常皮肤、基底细胞癌、无转移及有转移的鳞状细胞癌的阳性表达率分别为 10 0 %、81 8%、65 %及 2 1% ,其差别有显著意义 (P <0 0 5 )。结论　nm2 3 H1基因在非黑素性皮肤癌的浸润及淋巴结转移中起重要作用。     

CD44v6和nm23-H1在肺癌中的表达

[目的]研究CD44v6和nm23-H1蛋白在肺癌中的表达.[方法]对78例原发性肺癌采用S-P法进行免疫组化研究.[结果]CD44v6和nm23-H1蛋白表达在不同的肺癌临床分期、病理分化程度和淋巴结转移状况下均有显著差异,两者与肺癌的性别、年龄、肿块大小和病理类型均无关.[结论]CD44v6和nm23-H1检测可作为预测肿瘤转移潜能及预后的参考指标.     

新基因nm23-H1B在卵巢上皮性肿瘤中的表达研究

目的研究人类新基因nm23-H1B与卵巢肿瘤的关系。方法收集2003年4月~2004年2月手术切除各种卵巢肿瘤标本48例,正常卵巢组织8例。采用RT-PCR、Northern杂交、原位杂交检测nm23-H1BmRNA的表达。结果用RT-PCR在所有的标本中均检测到nm23-H1B基因mRNA的表达,其在正常卵巢组织中表达较低,而在所有的卵巢肿瘤中表达均出现明显上调,在早期卵巢癌中的表达高于晚期。Northern杂交显示nm23-H1B基因在正常卵巢组织的表达量较低,交界性肿瘤中的表达则与正常组织中相似,而在卵巢癌组织中表达明显增高,在早期卵巢癌中在分化好的组织中(Ⅰ级)表达量明显高于分化较差(Ⅱ、Ⅲ级)者。原位杂交显示nm23-H1B基因在正常卵巢组织和交界性肿瘤的表达量极低,而在卵巢癌组织中表达明显增高,mRNA表达产物主要位于细胞质内;早期卵巢癌中的mRNA表达量高于晚期卵巢癌。结论nm23-H1B基因与卵巢癌有明显的相关性。     

PCNA和nm23-H1在原发性肝癌中的表达及意义

目的探讨增殖细胞核抗原(PCNA)和抗癌基因nm23-H1蛋白产物与原发性肝癌的关系.方法用LSAB免疫组化法对41例原发性肝癌组织PCNA和nm23-H1蛋白产物进行检测.结果肿瘤组织的分化程度愈低,PCNA表达愈强,Ⅱ级以上的肿瘤表达强度100%.nm23-H1则相反,Ⅰ级66%阳性,Ⅱ级以上为14.6%.结论PCNA的表达强度可作为原发性肝癌的分级指标之一.nm23-H1的表达有助于了解肝癌的生物学行为和判断预后.     

核因子-κB和nm23-H1在肝细胞肝癌中的表达及其意义

目的探讨核因子NF-κB和转移抑制基因nm23-H1在肝细胞癌（HCC）组织的表达情况及与临床病理特征的关系。方法采用免疫组织化学方法检测41例HCC中NF-κB和nm23-H1的表达情况，以相应癌旁肝组织、肝硬化组织（10例）、肝血管瘤旁正常肝组织（11例）作对照，并分析其与病理特征的关系。结果NF-κB蛋白在41例HCC组织中阳性28例，表达率为68．3％；41例相应癌旁肝组织中有5例表达，阳性率12．2％，10例肝硬变组织中1例表达，11例正常肝组织未见表达，HCC与非癌组织中NF-κB蛋白的表达差异有统计学意义（χ^2=41．1，P〈0．01）；NF-κB的表达与HCC的临床病理特点无显著相关性。nm23-H1蛋白在41例HCC组织中14例为阳性染色，27例为阴性染色。nm23-H1阴性表达与肝被膜浸润和门静脉浸润显著相关（χ^2=4．16，χ^2=4．19，P均〈0．05）。结论NF-κB可能参与了HCC的发生、发展，可望作为基因治疗的靶点。nm23-H1在HCC中的阴性表达与HCC的恶性生物学特征相关，可能表明肿瘤的预后不良。     

nm23—H1蛋白和c-erbB-2蛋白在人肝细胞癌中的表达

应用免疫组化检测68例肝细胞癌（HCC）及其癌旁肝组织中nm23－H1蛋白和c－erbB－2蛋白的表达。结果显示nm23－H1蛋白在癌旁肝组织中均呈强阳性表达，肝细胞癌组织中38／68（56％）例呈阳性表达。阳性产物主要定位于肿瘤细胞胞浆，nm23－H1蛋白表达与HCC肿瘤体积、组织病理学分型及分级无关，而与肝内或肝外转移呈负相关。结果表明nm23-H1在抑制HCC肝内或肝外转移中起着重要作用。有可能成为评价HCC病人预后的一项指标。     

食管癌组织中nm23-H1蛋白表达及其临床意义

为探讨ｎｍ２３Ｈ１蛋白表达在食管癌中的临床意义，应用免疫组化ＳＰ法研究了６１例食管癌组织标本中ｎｍ２３Ｈ１蛋白表达与食管癌临床病理特征及预后的关系。ｎｍ２３Ｈ１蛋白阳性表达率为５４．１％（３３／６１），表达与性别、年龄、肿瘤部位、大小、病理类型及浸润程度无关。食管癌旁无淋巴结转移组ｎｍ２３Ｈ１阳性表达率为６１．５％（３２／５２），显著高于有转移组（１１．１％，１／９）。此外与术后肿瘤转移、复发有关，ｎｍ２３Ｈ１阳性表达组的术后生存时间明显长于ｎｍ２３Ｈ１阴性表达组（Ｐ＜０．０１）。结果表明：ｎｍ２３Ｈ１蛋白高表达对食管癌转移有一定的抑制作用，检测其表达有助于对食管癌生物学行为的了解和预后的判断。     

nm23-H1和MUC-1在外周T细胞淋巴瘤中的表达及其临床意义

背景与目的:外周T细胞淋巴瘤(peripheralT-celllymphoma,PTCL)是一类异质性疾病,临床侵袭性较强,常规治疗效果欠佳。国际预后指数(internationalprognosticindex,IPI)在PTCL中的价值尚未确定,有必要寻找一些分子指标来协助预测PTCL的预后。本研究旨在探讨nm23-H1和MUC-1对PTCL预后判断的价值。方法:免疫组化SP法检测中山大学肿瘤防治中心1997年1月至2004年12月间收治的96例初治PTCL患者组织中nm23-H1和MUC-1的表达情况,分析其表达与患者临床特征、近期疗效及远期生存率的关系。结果:96例患者nm23-H1和MUC-1的阳性率分别为81.2%(78/96)和58.3%(56/96);两者表达强度均与病理亚型无明显相关(P>0.05)。nm23-H1高表达与Ⅲ/Ⅳ期、PS状态≥2分、结外侵犯和结外病变数≥2等有关(P﹤0.05);而MUC-1高表达仅与分期Ⅲ/Ⅳ期、结外病变数≥2有关(P<0.05)。89例患者可评价化疗的客观疗效,全组有效率87.8%,完全缓解(CR)率56.7%。nm23-H1阴性者CR率高于阳性者(66.7%vs.55.4%,P<0.05),低表达组CR率高于高表达组(79.9%vs.44.0%,P<0.05);MUC-1阴性和低表达组的CR率分别高于阳性和高表达组,但均无显著性差异(P>0.05)。全组中位随访时间30个月(2～98个月),中位生存期32个月(95%CI26～34个月);nm23-H1阴性组5年生存率(overallsurvival,OS)明显高于阳性组(86.7%vs.24.9%,P=0.001),低表达组5年OS明显高于高表达组(52.3%vs.21.7%,P=0.000);MUC-1阴性组5年OS稍高于阳性组(47.9%vs.28.5%,P=0.260),低表达组5年OS稍高于高表达组(46.2%vs.22.2%,P=0.337)。多因素分析结果显示,IPI评分和nm23-H1表达水平是PTCL独立的预后指标。结论:nm23-H1在PTCL中过度表达提示预后不良,可作为判断PTCL预后的独立指标;MUC-1在PTCL中阳性及高表达与预后不良具一定的相关性,但对预后判断的价值尚不能确定。nm23-H1结合IPI评分等临床指标可能有助于更精确判断PTCL的预后。     

宫颈癌nm23-H1和MMP-9蛋白的表达及其临床意义

目的探讨宫颈癌组织中nm23-H1和MMP-9蛋白的表达及临床意义.方法采用免疫组化S-P法分析55例Ⅰ、Ⅱ期术后宫颈癌组织中nm23-H1和MMP-9蛋白的表达情况.结果nm23-H1和MMP-9在伴有淋巴结转移宫颈癌中的阳性表达率为27.3%和90.9%,无淋巴结转移为59.1%和61.4%,两组间差异有显著意义,P=0.041,P=0.032;nm23-H1和MMP-9表达与病理类型、组织分级和临床分期无明显相关.结论检测宫颈癌转移相关基因表达并分析其表达的相互关系有助于判断宫颈癌的转移潜能及指导术后干预治疗.     

Expression of nm23-H1 in transitional cell carcinoma of the upper urinary tract

Transitional cell carcinoma of the upper urinary tract is an uncommon neoplasm. Relatively little information is available regarding the clinical relevance of molecular markers. This study was performed to examine the importance of nm23-H1 gene expression (NM23-H1) in this type of tumors. Immunohistochemical expression of NM23-H1 was analyzed in 90 cases of upper urinary tract cancer, and was compared for its prognostic significance with conventional biological indicators. High expression of NM23-H1 was found in 7 cases (8%), intermediate expression in 32 cases (36%), and low expression in 51 cases (57%). Reduced NM23-H1 (defined as intermediate or low level of expression) was associated with a higher histological grading (p=0.002), invasive tumor growth (p=0. 002), or an increased proliferating cell nuclear antigen labeling index (p=0.004). NM23-H1 tended to inversely relate to later recurrence or long-term survival (p=0.06), but, only tumor staging was found to be significant in predicting clinical outcome (p=0.002). nm23-H1 appears to function as a tumor suppressor for upper urinary tract cancer, however, evaluation of NM23-H1 provides limited prognostic information.     

Expression of nm23-H1 gene product in nasopharyngeal carcinoma and its clinical significance

Objective: The nm23 gene is one of the tumor metastatic suppressor genes. The expression of nm23-H1 has been reported to be inversely associated with metastatic potentiality in a number of human carcinomas, including breast, colorectal, gastric, hepatocellular and gallbladder carcinomas. In this study, the immunohisto-chemical staining of nm23-H1 protein in human naso-pharyngeal carcinoma (NPC) was examined, and the relationship between nm23-H1 and both metastasis and prognosis of patients with NPC was also investigated. Methods: Routine LSAB immunohistochemistry with the nm23-H1 monoclonal murine antibody was employed to study the expression of nm23-H1 protein in 95 paraffin-embedded specimens of NPC treated at our hospital. The clinical pathologic data and results of follow-up were also retrieved. Comparisons between patients with and without expression of nm23-H1 protein with respect to metastasis, loco-regional recurrence and survival were performed using Log rank test. Multivariate prognostic analyses were performed by using Cox’s regression model. Results: Nm23-H1 negative expressive tumors were associated with a higher incidence of lymph-node metastasis (86.7%) than those of nm23-H1 positive (48.6%,P<0.01). Nm23-Hl negative expressive tumors were associated with a high incidence of recurrence and distant metastasis after radiotherapy (P<0.05). A significant association was found between expression of nm23-H1 and prognosis (P<0.01). The expression of nm23-H1 indicated favorable prognosis. Conclusion: It was suggested that nm23-H1 negative expression was significantly associated with lymph-node metastasis, recurrence and distant metastasis. Nm23-H1 may have value for predicting the prognosis of NPC.     

p53和nm23-H1在鼻咽癌组织中的表达及其意义

目的 探讨p53和nm23-H1蛋白在鼻咽癌中的表达及其与临床的相关性.方法 应用免疫组织化学方法对鼻咽癌40例、慢性鼻咽炎22例组织中p53和nm23-H1蛋白的表达进行检测,同时与临床相关资料进行对比研究.结果 慢性鼻咽炎组p53及nm23-H1蛋白的阳性率分别为1.0％、27.2％,而鼻咽癌组为92.5％、55.0％.在nm23-H1蛋白表达阳性的22例鼻咽癌组织中p53阳性表达9例（40.9％）,在nm23-H1表达阴性的18例中p53蛋白阳性表达17例（94.4％）.鼻咽癌组织中p53和nm23-H1蛋白的表达明显高于慢性鼻咽炎组织.p53蛋白表达与鼻咽癌淋巴结转移、临床分期和病理学分级呈正相关,与肿瘤T分级无关;nm23-H1蛋白表达与鼻咽癌淋巴结转移及临床分期呈负相关,与肿瘤T分级无关.结论 抑癌基因p53和nm23-H1在鼻咽癌的发生、发展及转移过程中起着协同、调控作用,可成为临床诊断和评价预后的重要生物学标志.