Nm23 expression in human gastric cancers - possible correlation of nm23 with lymph-node metastasis

In order to elucidate the relationship between nm23 and metastasis in human gastric cancers, we analyzed gene and protein expression of nm23-H1 using Northern blot and immunohistochemical techniques. nm23-H1 gene expression was identified in 17 out of 19 gastric cancer tissues. The signals in the tumor tissues presenting regional lymph node metastasis seem to be lower than those in the tumor tissues without regional lymph node metastasis, suggesting a role of nm23-H1 in the regional lymph node metastasis in the gastric cancers. However, the protein expression detected immunohistochemically was not correlated to the gene expression, partly because of difficulty in quantifying the amount of protein. Expression of the nm23-H1 gene as well as the nm23-H1 protein in the tumor tissues was higher than those in the corresponding normal mucosae. This suggests a linkage of nm23-H1 in the process of the gastric cancer progression. We also analyzed the sequence abnormalities of the nm23-H1 gene in the gastric cancer tissues using a direct sequencing technique, no mutations were observed.     

Differential expression of metastasis-associated genes in papilla of vater and pancreatic cancer correlates with disease stage.

PURPOSE: Papilla of Vater cancer has a much better prognosis than pancreatic cancer. It is not known whether this is the result of differences in the tumor biology of the two malignancies. Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic cancer. PATIENTS AND METHODS: Analysis was performed in nine normal human papilla of Vater samples, 27 papilla of Vater cancers, 16 normal pancreatic samples, and 29 pancreatic cancers. Expression of nm23-H1 and KAI1 was analyzed by Northern blot analysis and in situ hybridization. In addition, immunohistochemistry was performed to localize the respective proteins. RESULTS: There was no difference in nm23-H1 and KAI1 mRNA expression levels in normal versus cancerous papilla of Vater samples. In contrast, nm23-H1 and KAI1 RNA expression was upregulated in early tumor stages of pancreatic cancer and reduced in advanced tumor stages. When expression of nm23-H1 and KAI1 RNA was analyzed by use of in situ hybridization, normal epithelial cells of the papilla of Vater exhibited mRNA staining intensity similar to that of papilla of Vater cancer cells. Similar levels of nm23-H1 and KAI1 immunoreactivity also were observed in these samples. In contrast, early stage pancreatic cancer samples exhibited stronger nm23-H1 and KAI1 immunoreactivity than normal controls. Furthermore, early pancreatic cancer stages exhibited higher KAI1 and nm23-H1 immunostaining than advanced tumor stages. CONCLUSION: Differences in the expression patterns of the two tumor suppressor genes nm23-H1 and KAI1 may contribute to the different prognoses of papilla of Vater cancer and pancreatic cancer. Our findings support the hypothesis that biologic differences rather than earlier diagnosis influence the different outcomes of these two tumor entities.     

Reappraisal of the role of NM23-H1 in colorectal cancers

BACKGROUND AND OBJECTIVES: A number of evidence indicate that downregulation of the nm23-H1 gene may be relevant to metastatic progression of many kinds of human cancer. However, its role in colorectal cancers remains controversial. To address the issue, this study was performed to investigate the clinical relevance of nm23-H1 in patients with colorectal cancers. METHODS: Immunohistochemical expression of nm23-H1 protein product (NM23-H1) was studied in a total of 146 colorectal cancer patients and compared for its prognostic value at a mean follow-up of 54 months. RESULTS: There was no apparent correlation between NM23-H1 expression and clinicopathological indicators, including Dukes category, lymphatic metastasis, distant metastasis, histological grading, and tumor location (P < 0.1, respectively). In addition, determination of NM23-H1 expression status did not provide independent prognostic information compared with conventional pathological staging. CONCLUSIONS: The results indicate that nm23-H1 gene does not play an important part in the progression of colorectal carcinogenesis.     

nm23-H_1mRNA表达与肾母细胞瘤临床行为的关系

应用Northernblot分子杂交技术，检测30例肾母细胞瘤及其对应正常肾组织中nm23－H1mRNA表达。通过nm23－H1mRNA水平的比较及其与临床病理的分析，发现肾母细胞瘤nm23－H1mRNA呈低表达，随着病程的演进和转移的出现，肿瘤细胞中nm23－H1mRNA表达水平呈显著性降低，与肿瘤的病理类型无显著相关性（P＞0．05）。提示nm23－H1RNA低表达可能是肾母细胞瘤演进和转移的重要因素。     

The role of nm23-H1 in the progression of transitional cell bladder cancer.

The nm23 gene was initially cloned as a metastasis suppressor gene, but the clinical relevance of nm23-H1 as a metastasis suppressor or prognostic indicator for human cancers remains enigmatic. Given that gene expression is regulated at the tissue-specific level, we studied the molecular mechanisms of nm23-H1 expression in human bladder cancer cell lines and the clinical importance of protein product (NM23-H1) in association with patient outcome (n = 257) by immunohistochemistry. We demonstrated that nm23-H1 is expressed in bladder cancer cells without genomic alterations. High NM23-H1 expression was found in 39 cases (15.2%), intermediate expression in 119 cases (46.3%), and low NM23-H1 in 99 cases (38.5%). NM23-H1 was inversely related to staging classification or tumor size (P < 0.05), with the most significant difference being observed between pTa tumors and those of pT1-pT3 bladder cancer (P = 0.01). Reduced NM23-H1, defined as intermediate and low levels of expression, tended to have a higher risk of tumor metastasis (P = 0.06) or poor longtime survival (P = 0.07). In the subset of grade 2 bladder tumors, reduced NM23-H1 significantly correlated with the occurrence of tumor metastasis or poor patient survival (P < 0.05). These findings overall suggest that nm23-H1 may play an important role in suppressing the early step of carcinogenesis and thus act as an invasion suppressor for human bladder cancer. A prospective study is required to clarify the potential of the molecular marker in prediction of disease progression.     

nm23-H1 protein immunohistochemical expression in human breast cancer

A series of 76 patients undergoing surgery for primary breast carcinoma has been prospectively studied in order to evaluate the relative weight of nm23-H1 protein expression in disease-free survival. Expression of nm23 protein was immunohistochemically assessed. In all, 39% (29/74) of the turners showed positive staining for nm23-H1 protein expression. Negative nm23-H1 expression was found in poorly differentiated, tumors (p<0.02). There was no significant relationship between nm23-H1 and the other clinicopathological and biological features examined. In the univariate statistical analysis, node positivity, G3 histological grade and high flow cytometric S phase fraction (SPF) value proved to be significantly related to risk of relapse. In the multivariate analysis, only histological grade (G3) and high SPF values (>10.6) proved to be independently related to risk of relapse, with a hazard ratio of 9.84 and 7.98 respectively. Our preliminary study suggests that immunohistochemical nm23-H1 expression should not be considered a marker for predicting tumor progression and patient prognosis.     

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.     

p53和nm23-H1蛋白表达与食管癌浸润转移的关系

Objective To study the relationship between expression of p53 and nm23-H1 and differentiation, invasiveness and metastasis in human esophageal carcinoma, and the correlation between expression of p53 and nm23-H1. Methods Expression of p53 and nm23-H1 in 50 patients with squamous cell carcinoma of esophagus was detected by using immuno-histochemical S-P methods. Results 35 cases (70%) and 32 cases (64%) of esophageal squamous cell carcinoma were positive for nm23-H1 protein and p53 protein, respectively. The expression of nm23-H1 was related to lymphatic metastasis (P<0.025), but not related to tumor differentiation, invasiveness, tumor location, tumor length, patient's gender and age (P>0.05). The lymphatic metastasis location positive group had a very lower expression of nm23-H1 and the negative rate was 70.8%, but the negative group had a higher expression and the positive rate was 65.4%. The expression of p53 was related to tumor differentiation and invasiveness (P<0.05), but not related to lymphatic metastasis, tumor location, tumor length, patient's gender and age(P>0.05). Among the three groups, the high differentiation group had the lowest expression of p53 and the positive rate was 29.2%, but the low differentiation group had the highest positive rate (71.4%). As for tumor invasiveness, the group of outer membrane of esophagus infiltrated had the highest p53 protein positive rate (56%), but in the group, of mucous or submucous layer infiltrated p53 protien was not detectable. The low expression of nm23-H1 and the high expression of p53 were also correlated. The expression of nm23-H1 and p53 were both correlated with TNM stage of esophageal carcinoma (P<0.05). The better esophageal carcinomas differentiated, the lower nm23-H1 expressed and higher p53 expressed. Conclusion Low expression of nm23-H1 and high expression of p53 play an important role in the progression of squamous cell carcinoma of esophagus. Nm23-H1 might beta gene markef in the prophecy of patients' prognosis and benefit tumor treatment clinically.     

食管鳞状细胞癌中nm23-H1和p53蛋白表达及其相互关系

目的:探讨食管鳞癌组织中p53和nm23-H1蛋白的表达与癌组织分化浸润转移的关系,以及探讨两者之间的相关性,并进一步分析癌组织中p53和nm23-H1蛋白表达对食管癌患者的预后意义。方法:采用免疫组织化学(S-P法)方法对100例人食管鳞癌组织中的p53和nm23-H1蛋白的表达情况进行检测。结果:100例食管鳞癌组织中,nm23-H1阳性表达者70例(阳性率为70%),p53阳性表达者64例(阳性率为64%)。nm23-H1蛋白表达与食管癌淋巴结转移有关(P<0.025),与食管鳞状细胞癌的分化程度、肿瘤部位、浸润深度、病变长度以及患者性别、年龄无关(P>0.05)。p53蛋白表达与食管鳞状细胞癌的分化程度、浸润深度有关(P<0.05),与食管癌淋巴结转移、肿瘤部位、病变长度、患者性别、年龄无关(P>0.05)。高分化鳞癌组织中p53明显低表达(29.2%);低分化鳞状细胞癌组织中p53表达明显增高(71.4%)。食管外膜受累者p53表达较高(56%);仅发生食管粘膜和(或)粘膜下浸润组的癌组织中未发现有p53蛋白的表达。食管癌组织中nm23-H1蛋白低(高)表达与p53高(低)表达之间有明显相关性(P<0.01)。nm23-H1和p53蛋白表达亦与食管癌的TNM分期密切相关(P<0.05)。食管癌TNM分期越晚,其癌组织中nm23-H1蛋白表达越低,p53蛋白表达越高。结论:nm23-H1基因低表达与p53基因高表达可能在食管鳞状细胞癌浸润转移过程中发挥重要作用。nm23-H1可以作为食管鳞状细胞癌患者预后的基因标记,其蛋白表达产物的检测可以用于患者预后的判断,并为患者治疗方案的制定提供参考。     

Expression of nm23 protein in adult soft tissue sarcoma is correlated with histological grade

BACKGROUND: There is controversy about whether expression of nm23 is involved in suppression of metastases or contributes to tumour progression. Few studies have examined the role of nm23 in sarcomas. The aim of this study was to determine if expression of nm23 protein or its H1-subtype correlated with clinicopathological parameters in adult soft tissue sarcomas (STS). MATERIALS AND METHODS: Protein expression was examined by immunohistochemistry on paraffin-embedded sections of 46 STS patients, quantified using a colour video imaging system and correlated to histological grade. The monoclonal antibodies used were anti-nm23 (recognising both nm23-H1 and nm23-H2) and anti-nm23-H1 (recognising nm23-H1 only). RESULTS: High-grade tumours significantly overexpressed nm23 (including both nm23-H1 and nm23-H2) compared with both intermediate and low-grade tumours (ANOVA and Tukey, all p < 0.05). Multiple regression analysis confirmed the significance of the relationship and independence of the nm23 (p = 0.005), but not nm23-H1. CONCLUSION: Expression of nm23 protein, particularly nm23-H2, is an independent predictor of malignant potential of adult STS.     

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.     

nm23—H1基因在大肠癌中的表达与肝转移及预后的关系

目的：探讨ｎｍ２３－Ｈ１蛋白表达与大肠癌肝转移及预后的关系。方法：对１０１例大肠癌存档石蜡块进行重新切片，采用ｎｍ２３－Ｈ１单克隆抗体进行免疫组化染色（ＬＳＡＢ法）。结果：ｎｍ２３－Ｈ１蛋白表达与年龄、性别、肿瘤大小、部位、组织类型、浆膜侵犯无关；与Ｄｕｋｅｓ分期、淋巴结转移有关；手术时有肝转移组较无肝转移组低，手术后有肝转移复发组较无肝转移复发组低（Ｐ＜００１）。Ｃｏｘ模型分析显示ｎｍ２３－Ｈ１是大肠癌预后的一个保护性指标。结论：ｎｍ２３－Ｈ１基因对大肠癌肝转移和预后具有重要作用。ＬＳＡＢ法检测大肠癌组织中ｎｍ２３－Ｈ１蛋白表达可能是预测大肠癌肝转移及预后的生物学指标之     

nm23－H1和CD44蛋白在鼻咽癌中的表达及其与临床的关系

目的：探讨鼻咽癌（ＮＰＣ）中ｎｍ２３－Ｈ１和ＣＤ４４的表达及其与临床的关系。方法：收集ＮＰＣ蜡块标本,应用免疫组化ＬＳＡＢ法,检测ｎｍ２３－Ｈ１和ＣＤ４４基因蛋白的表达,其中前者４８例,后者４０例,３７例同时进行了上述两种检测,将两种基因蛋白表达结果与其临床的关系进行研究分析。结果：ｎｍ２３－Ｈ１阳性表达率６０．４２％,其与颈淋巴结转移无关,但与转移之颈淋巴结大小有关;ｎｍ２３－Ｈ１的表达与放疗后     

Expression of nm23-h1 gene in squamous-cell carcinoma of the cervix correlates with 5-year survival

We have examined nm23-H1 protein levels in human squamous cell carcinoma of the cervix by immunohistochemistry and correlated detectable nm23-H1 with patient survival. Normal cervical tissue samples were consistently strongly immunoreactive. In contrast, cervical carcinomas stained poorly, if at all. Well differentiated carcinomas stained more frequently for nm23-H1 protein than poorly or undifferentiated carcinomas. Our results clearly demonstrated a significant correlation between absence of nm23-H1 protein staining and shorter survival of patients with cervical cancer. Our results suggest that nm23 may serve as a potentially valuable prognostic marker for this type of tumor and to our knowledge is the first report of this kind for cervical carcinoma.     

Immunohistochemical Analysis of nm23/NDP Kinase Expression in Human Lung Adenocarcinoma: Association with Tumor Progression in Clara Cell Type

Levels of nm23-H1/nucleoside diphosphate kinase (NDP kinase) expression have been reported to correlate inversely with mctastatic potential in some tumors but not in others. Whether or not nm23 gene product is associated with metastatic potential in lung cancer is not clear as yet. We therefore immunohistochemically examined the expression of nm23 gene products in primary lung adenocarci-no mas according to cytologic subtypes in order to clarify the association of its expression with the clinical features of the disease. Seventy-two (64.9%) of the 111 lung adenocarcinomas were positive for nm23 protein. In lung adenocarcinoma of Clara cell type, high levels of nm23 expression were associated with advanced pathologic stage, positive lymph node status, and poorer prognosis (P<0.05). However, no correlation with clinical outcome was observed in other cell types. Our data suggest that higher levels of nm23 expression are associated with tumor progression in lung adenocarcinoma of Clara cell type.     

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。     

大小肝癌中相关因子的表达差异及其意义

目的:比较影响大、小肝癌生物学行为差异的相关因素,并探讨其可能的机制。方法:采用免疫组化方法检测nm23-H1、c-Met、MT1-MMP(membrane-type1matrixmetalloproteinase)、Ki-67蛋白在53例大肝癌(瘤体直径>3cm)及40例小肝癌(单肿瘤结节,瘤体直径≤3cm)中的表达,并分析其与肝癌临床病理因子的关系。结果:nm23-H1、c-Met、MT1-MMP蛋白在大、小肝癌组织中的表达差异显著(分别为P=0.005、P=0.008和P=0.007);nm23-H1蛋白表达与肿瘤远处转移之间呈负相关关系(P=0.041);c-Met、MT1-MMP蛋白表达与肿瘤包膜浸润、远处转移之间均呈正相关关系(P<0.05)。结论:大肝癌组织表达nm23-H1、c-Met、MT1-MMP蛋白发生改变,是促使其生物学行为较小肝癌更为恶性的重要因素。