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。     

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.     

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.     

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.     

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。     

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.     

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     

Correlation between nm23-H1 overexpression and clinicopathological variables in human anal canal carcinoma.

To improve life expectancy prognostic factors other than TNM have been investigated. It is thought that nm23 protein may play a specific biological role in suppressing tumor metastasis. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma. Immunostaining using anti-nm23 monoclonal antibody was performed in 22 anal canal tumors. The results were correlated with clinicopathological variables. Six cases out of 22 (27.3%) were nm23-positive. Significant association was found between nm23-H1 expression and depth of invasion, lymph node involvement and prognosis (p<0.05). There was no significant association between nm23-H1 expression, histologic type and age of the patients. nm23-H1 expression was not seen in our cases with metastasis and this may be related to nm23 gene alterations not being detectable by the monoclonal antibody used or to the presence of a subset of tumors in which nm23 gene abnormalities had not yet occurred at the time of tumor excision or biopsy. Overexpression of nm23-H1 protein in anal canal carcinoma may have implications for its metastatic potential. nm23-H1 expression would provide a more accurate evaluation of outcome for individual patients and thus improve treatment planning.     

nm230-H1、p16抑癌基因蛋白在甲状腺肿瘤中的表达及其临床意义

 目的 探讨抑癌基因nm23－H1及p16与甲状腺癌的发病学及其生物学行为的关系.方法 应用SP免疫组化方法 检测了54例甲状腺癌、16例腺癌、10例甲状腺非瘤病变的nm23－H1、p16基因蛋白的表达。结果 甲状腺腺瘤及分化型甲状腺癌中的nm23－H1及p16表达率及表达强度均显著增强（P＜0．05）,而甲状腺未分化癌中nm23－H1及p16表达率及表达强度则显著降低（P＜0．01）。nm23－H1及p16蛋白表达与甲状腺癌的分化程度呈正相关（P＜0．01）,与预淋巴结转移无显著相关性,但nm23－H1与包膜侵犯呈负相关（P＜0．05）。结论 nm23－H1及p16基因失活与甲状腺未分化癌的发生密切相关,可为临床判断恶性程度及生物学行为提供参考。     

PTEN及nm23-H1蛋白表达在非小细胞肺癌转移中的意义

背景与目的PTEN及nm23-H1基因均被证实是肿瘤转移的抑制基因,目前大多数研究都停留在基础研究上,本研究通过检测PTEN及nm23-H1蛋白在非小细胞肺癌(NSCLC)中的表达,以探讨它们的临床意义及相互关系。方法应用免疫组织化学法检测60例非小细胞肺癌组织中PTEN及nm23-H1基因蛋白的表达。结果NSCLC无淋巴结转移组PTEN蛋白阳性表达率为79.31%,高于NSCLC伴有淋巴结转移组41.94%,两者差异有统计学意义(P<0.01);无淋巴结转移组nm23-H1蛋白阳性表达率为82.76%,高于NSCLC伴有淋巴结转移组45.16%,两者差异有统计学意义(P<0.01)。PTEN和nm23-H1蛋白表达在NSCLC中一致性较好(Kappa=0.4366,Z=3.3905,P<0.01),两基因可能有协同作用。结论PTEN及nm23-H1蛋白表达均与NSCLC的淋巴结转移有关,PTEN和nm23-H1蛋白均可作为预测肿瘤转移的重要指标,对两种蛋白进行免疫组织化学联合检测,可能更有利于肺癌预测淋巴结转移及预后。     

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.     

MTA1和nm23-H1蛋白表达与乳腺癌生物学行为之间的关系

目的探讨肿瘤转移相关基因（NTA1）和nm23-H1蛋白表达与乳腺癌生物学行为之间的关系。方法运用免疫组化S-P法检测56例乳腺癌组织中NTAl、nm23-H1蛋白的表达。结果56例乳腺癌组织中39例NTA1蛋白阳性表达，阳性率为69．6％，NTA1高表达与乳腺癌组织学分级、临床分期和淋巴结转移关系密切（P〈0．05）；3l例nm23-H1蛋白阳性表达，阳性率为55．4％，nm23-H1低表达与乳腺癌组织学分级、临床分期和淋巴结转移关系密切（P〈0．05）；乳腺癌组织中NTA1、nm23-H1蛋白表达呈负相关（P〈0．05）。结论NTA1和nm23-H1蛋白表达与乳腺癌分化程度、淋巴结转移和预后关系密切，可作为诊断乳腺癌患者转移复发的参考指标，并有望成为乳腺癌基因治疗的新靶点。     

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.     

NM-23 H1 immunohistochemistry is not useful as predictor of metastatic potential of colorectal cancer.

This study aimed to investigate whether immunohistochemical staining for nm23-H1 protein in the primary tumour is correlated with tumour stage, tumour differentiation, DNA ploidy, cell proliferative index, p53 status and patient survival time in colorectal cancer. Full-cross colorectal cancer biopsies were collected from 202 consecutive surgical specimens between 1987 and 1990. Immunohistochemical expression of nm23-H1 protein was investigated in cryosections, using a monoclonal anti-nm23-H1 antibody (clone NM 301). The staining pattern was classified as follows: strong homogeneous intensity, moderate homogeneous intensity, moderate focal intensity, or as negative. Immunohistochemical expression of p53 was investigated using a monoclonal anti-p53 antibody (DO-7). The DNA ploidy and cell proliferative index were determined by flow cytometry. Possible correlation between nm23-H1 staining patterns and the other studied tumour characteristics was explored at the end of 1994. Median survival time of living patients was 66 months, range 50-93 months. No correlation was found between various nm23-H1 staining patterns and tumour stage, cell proliferative index or p53 status. Nm23-H1-negative tumours and tumours with moderate focal staining intensity were less differentiated than tumours with strong homogeneous or moderate homogeneous staining intensity (P < 0.05). Of the nm23-H1-negative tumours, a significantly higher number was near-diploid rather than aneuploid, as compared with those expressing positive nm23-H1 (P < 0.05). The number of dead patients in Dukes'' stages B and C did not correlate significantly with the nm23-H1 staining pattern. The nm23-H1 staining pattern alone, or combined with either of the other explored tumour characteristics, did not correlate with patient survival time. Immunohistochemical studies of the nm23-H1 protein expression are of minor value in the staging and prognostic prediction of colorectal cancer.     

乳腺癌组织中p53、nm23-H1基因表达及其与绝经状态、淋巴结转移的相关性

[目的]研究乳腺癌患者中p53和nm23-H1基因表达,及其与绝经状态及腋窝淋巴结转移的关系.[方法]采用免疫组织化学SP方法检测60例乳腺癌组织中p53和nm23-H1的表达.[结果]60例乳腺癌患者中,p53和nm23-H1的阳性表达率分别为73.3%(44/60)和66.7%(40/60);在绝经前患者中p53和nm23-H1的阳性表达率分别为66.7%(16/24)和50.0%(12/24),而在绝经后患者中两者的阳性表达率分别为77.8%(28/36)和77.8%(28/36).在绝经后患者中p53和nm23-H1基因的阳性表达与腋窝淋巴转移呈显著性相关(P=0.019和P=0.019).[结论]p53可能参与绝经前妇女乳腺癌的发生,可能促进绝经后乳腺癌的转移;而nm23-H1可能参与绝经后乳腺癌的转移.     

Breast-cancer in the elderly - detection and treatment modalities in 341 women

We examined nm23-H1 protein levels in human oligodendrogliomas by immunohistochemistry. This class of brain tumor does not form spontaneous metastases, but its progression from benign (oligodendroglioma) toward malignant phenotype (oligodendroglioma transitionale and glioblastoma oligodendrogliale) can be followed. Two types of tumors, ODG-II and ODG-T, were highly positive for nm23 protein. However, there was no clear correlation between the extent of protein expression and tumor aggressiveness. No nm23 protein was detected in nonproliferative normal brain tissues and was found in only a few ODG-I specimens. As cell proliferation becomes more pronounced (OGD-II, ODG-T), nm23 protein becomes detectable in almost all samples. However, of the glioblastoma oligodendrogliale samples examined, 76% were negative for nm23-H1 protein. suggesting a change in nm23-H1 gene expression with increasing neoplastic progression. Our findings are in contrast to a proposed role of nm23-H1 protein as a tumor metastasis suppressor and support that it cannot serve as a reliable prognostic tumor indicator in all cases. However, our findings may contribute to a better understanding of glial tumor development and improve the accuracy of tumor diagnosis.     

120例胃癌中p16,nm23—H1基因蛋白表达与临床预后的关系

应用ＬＳＡＢ免疫组化法对１２０例胃癌组织中，ｐ１６，ｎｍ２３－Ｈ１基因蛋白测定，结果发现，ｐ１６和ｎｍ２３－Ｈ１，阳性表达率分别为４８．３％，２９．２％。二者共同阳性为２２．５％，ｐ１６，ｎｍ２３－Ｈ１阳性病例存活率明显高于阴性病例（Ｐ〈０．０１），ｐ１６、ｎｍ２３－Ｈ１阳性病例存活率明显高于阴性病例（Ｐ〈０．０１），结果提示ｐ１６，ｎｍ２３－Ｈ１在胃癌中的阳性表达对抑制肿瘤生长、浸润和转移起了重     

Prognostic significance of nm23-H1 expression in oral squamous cell carcinoma

Recent studies indicated nm23-H1 played a role in cancer progression. Therefore, we investigated clinical significance of nm23-H1 expression in oral squamous cell carcinoma (OSCC). In total, 86 OSCC specimens were immunohistochemically stained with nm23-H1-specific monoclonal antibodies. Immunohistochemical staining of nm23-H1 was confirmed by immunoblotting. The relations between nm23-H1 expression and clinicopathologic variables were evaluated by chi(2) analysis. As increased size of primary tumour could escalate metastatic potential and the data of patients at the late T stage might confound statistical analyses, we thus paid special attention to 54 patients at the early T stage of OSCC. Statistical difference of survival was compared by a log-rank test. Immunohistochemically, nm23-H1 expression was detected in 48.8% (42 out of 86) of tumorous specimens. It positively correlated with larger primary tumour size (P=0.03) and inversely with cigarette-smoking habit (P=0.042). In patients at the early T stage, decreased nm23 expression was associated with increased incidence of lymph node metastasis (P=0.004) and indicated poor survival (P=0.014). Tumour nm23-H1 expression is a prognostic factor for predicting better survival in OSCC patients at the early T stage, which may reflect antimetastatic potential of nm23. Therefore, modulation of nm23-H1 expression in cancer cells can provide a novel possibility of improving therapeutic strategy at this stage. In addition, our results further indicated cigarette smoking could aggravate the extent of nm23-H1 expression and possibly disease progression of OSCC patients.     

大肠癌中nm23-H1的表达与淋巴结转移的关系

 目的　探讨大肠癌中nm23-H1的表达与淋巴转移的关系。方法　应用免疫组化方法研究96例大肠癌中nm23-H1蛋白的表达。结果　nm23-H1蛋白低表达与淋巴结或远处转移显著相关(P<0.05);nm23-H1蛋白低表达预测大肠癌转移的灵敏性为88.4%,特异性为79.3%。结论　检测nm23-H1蛋白可以预测大肠癌淋巴结或远处转移,从而可能成为临床治疗的判断依据。