Nm23 Expression Research Articles

The role of NM23 in patients with colorectal cancer: A systematic review and meta-analysis.

This meta-analysis was carried out to evaluate the relationship between NM23 expression and the prognosis of patients with colorectal cancer. We searched PubMed, EMBASE and Web of Science for relevant articles. The pooled odd ratios (ORs) and corresponding 95%CI were calculated to evaluate the prognostic value of NM23 expression in patients with colorectal cancer, and the association between NM23 expression and clinicopathological factors. In total, 2289 patients were pooled from 24 available studies. The incorporative OR combined by 16 studies with overall survival showed that high NM23 expression was associated with better overall survival (OR=0.67, 95%CI: 0.49-0.93, P=0.02, I 2=56%, Ph=0.004). And a new estimate without heterogeneity was produced when only combining high-quality studies (OR=0.70, 95%CI: 0.56-0.86, P=0.0007, I 2=46%). In disease free survival (DFS), we also obtained a good prognosis (OR=0.30, 95%CI: 0.14-0.68, P=0.004). Although we failed to find any significance in N status (P=0.10), elevated NM23 expression was related to well tumor differentiation (OR=0.60, 95%CI: 0.44-0.820, P=0.001) and Dukes' A&B (OR=0.55, 95%CI: 0.32-0.95, P=0.03). These results indicated that over-expressed NM23 might be an indicator of good prognosis, well tumor differentiation and Dukes' A&B of patients with colorectal cancer, but no significance was found in N status.

Prognostic value of epidermal growth factor receptor and nm23 expression in patients with rectal cancer and its guiding significance for treatment

Objective To evaluate the predictive value of epidermal growth factor receptor (EGFR) and nm23 expression and its guiding role of choosing chemotherapy regimen in post-operation patients with rectal carcinoma. Methods The expression of EGFR and nm23 in 243 specimens of rectal carcinoma tissues was examined by immunohistochemistry. The clinical and pathological data were recorded, and patients were followed up for more than five years. Kaplan-Meier estimates, Cox proportional hazard regression and hierarchical analyses were employed to assess the correlation between the expression of EGFR and nm23 in rectal carcinoma and the progression free survival (PFS) of patients treated with the different surgical methods and chemotherapy. Results EGFR and nm23 were expressed proportionately in rectal cancer tissues. Kaplan-Meier showed that EGFR expression is negatively related to the PFS of the post-operative patients. The median PFS was 21.0 months in the patients with high expression, and that was 37.8 months in the patients with low expression (χ2=8.687, P=0.003). The nm23 expression was positively associated with the PFS of the post-operative patients. The median PFS was 35.4 months in the patients with high expression, and that was 13.4 months in the patients with low expression (χ2=15.593, P=0.001). The median PFS was longer in the patients with low EGFR expression and high nm23 expression (median PFS=62.9 months, χ2=18.227, P=0.000). The univariate analyses revealed that the patients with low EGFR expression and high nm23 expression had longer PFS than in those with high EGFR expression and low nm23 expression[hazard ratio (HR)=2.290, 95% confidence interval (CI): 1.548-3.387, P=0.000]. Multivariate analysis (Cox) showed that low EGFR expression and high nm23 expression was an independent combined predictor of longer PFS (HR=1.966, 95%CI: 1.319-2.929, P=0.001). In addition, hierarchical analysis also suggested that post-Dixon operation patients with low EGFR expression and high nm23 expression had significantly longer survival time than other patients, and also were more sensitive to chemotherapy with FOLFOX4 regimen than other patients (median PFS=61.1 months, χ2=8.218, P=0.004). Conclusion EGFR and nm23 have predictive value for the prognosis of post-operative patients with rectal carcinoma and are an ideal combination of predictive factors. Key words: Epidermal growth factor receptor; nm23; Rectal carcinoma

Meta-Analysis of the Relationship between NM23 Expression to Gastric Cancer Risk and Clinical Features.

The prognostic value of reduced NM23 expression for gastric cancer (GC) patients is still contradictory. Thus, we conducted a meta-analysis to quantitatively evaluate the association of NM23 expression with GC risk and clinical features by analyzing 27 publications. The result of our meta-analysis indicated that NM23 expression is markedly reduced in gastric cancer tissues (OR = 3.15; 95% CI = 1.97–5.03; P < 0.001). Furthermore, NM23 expression was negatively correlated with N stage, TNM stage, and histological grade. However, NM23 expression was not correlated with T stage, lymphatic invasion, vascular invasion, and 5-year overall survival rate. In conclusion, reduced NM23 expression correlated with gastric cancer risk, but its association with GC clinical features remains inconclusive. Therefore, large-scale and well-designed studies, which use uniform antibody and criterion of NM23 positive expression, are required to further validate the role of the NM23 in predicting GC progression.

Prognostic and clinicopathological value of NM23 expression in patients with breast cancer: A systematic review and meta-analysis

It is hypothesized that, NM23, as a metastasis suppressor gene, may be a good indicator of patients with breast cancer in most reports. The aim of our meta-analysis was to determine the prognostic value of NM23 in patients with breast cancer synthetically, by searching 3 databases, PubMed, EMBASE, and Web of Science, for relevant articles. The inclusion criteria, exclusion criteria, and the standard-of-quality assessment were used according to a previous protocol. The pooled odd ratios (ORs) and corresponding 95% CI were calculated to assess the primary end point, survival data, and the secondary end point, associations between NM23 expression and clinicopathological factors. Finally, funnel plots and Egger׳s linear regression test were used to assess the potential publication bias. Overall, 792 articles were retrieved in the initial search of databases, and 4968 patients were eventually pooled from 26 available studies selected out by 2 independent reviewers. The incorporative OR showed that elevated NM23 expression was associated with better overall survival (OR = 0.62; 95% CI: 0.52-0.74; P < 0.00001; I2 = 0%; Ph = 0.46). In disease-free survival, we also obtained a good prognosis (OR = 0.30; 95% CI: 0.18-0.48; P < 0.00001; I2 = 46%; Ph = 0.13). In addition, high-NM23 expression was correlated with well or moderate histologic grade, negative lymph node metastasis, and early tumor staging. Furthermore, publication bias was detected in overall survival but not in disease-free survival, and it could also be verified by Egger׳s test (P = 0.009 and P = 0.687, respectively). These results implied that NM23 might be an indicator of good prognosis in patients with breast cancer, although further researches need to be performed to confirm the prognostic value of NM23.

Hierarchical investigating the predictive value of p53, COX2, EGFR, nm23 in the post-operative patients with colorectal carcinoma.

The aim of this study was to evaluate the correlations between p53, COX2, EGFR, nm23 expression and the progression free survival (PFS) of post-operative patients with colorectal carcinoma. Immunohistochemistry was used to detect the expression of p53, COX2, EGFR and nm23 in 459 specimens from colorectal carcinoma patients. Kaplan-Meier estimates, Cox proportional hazard regression analyses and hierarchical analyses were performed on the collected data. Kaplan-Meier estimates analysis suggested that EGFR expression was as a negative predictor, the median PFS of patients with EGFR high expression was 21.73 months, and the median PFS of patients with low EGFR expression was 57.83 months (χ2=20.880, P<0.001); nm23 expression was positive predictive factor for the prognosis of patients with colorectal carcinoma, the median PFS of patients with high nm23 expression was 37.77 months, and the median PFS was 21.47 months in the patients with low nm23 expression (χ2=7.364, P=0.007). Cox regression analysis revealed that comparing with the patients with low expression of EGFR, the patients with high EGFR expression were at higher risk of tumor progression (HR=1.667, P=0.004); Comparing with the patients with high nm23 expression, the patients with nm23 low expression had a higher risk of tumor progression (HR=0.412, P<0.001); and the risk of tumor progression was higher in the patients with high EGFR expression and low nm23 expression (HR=0.245, P<0.001). Hierarchical analysis showed that EGFR expression mainly correlates with the PFS of TNM stage I-II colorectal cancer patients, the median PFS was 33.53 months in the TNM stage I-II colorectal cancer patients with high EGFR expression patients; The median PFS of the TNM stage I-II colorectal cancer patients with low EGFR expression was 70.43 months (χ2=9.530, P=0.002); The median PFS was 19.2 months in the TNM stage III-IV colorectal cancer patients with high expression EGFR, the PFS of the TNM stage III-IV colorectal cancer patients with low EGFR expression was 37.87 months (χ2=7.97, P=0.005). nm23 expression mainly correlates with the PFS of TNM stage III-IV colorecatal cancer patients. The median PFS was 47.27 months in TNM stage I-II colorectal cancer patients with nm23 high expression, the median PFS was 48.85 months in TNM stage I-II colorectal cancer patients with low nm23 expression (χ2=0.101, P=0.750); The median PFS was 28.8 months in TNM stage III-IV colorectal cancer patients with nm23 high expression, the median PFS was 14.7 months in TNM stage III-IV colorectal cancer patients with low nm23 expression (χ2=13.213, P<0.001). EGFR is mainly a predictive factor for the prognosis of post-operative patients with TNM stage I-II colorectal cancer, and nm23 is important for predicting the prognosis of patients with stage III-IV, and EGFR and nm23 could be as predictor of combination.

Nm23 regulates decidualization through the PI3K-Akt-mTOR signaling pathways in mice and humans.

Does nm23 have functional significance in decidualization in mice and humans? nm23 affects decidualization via the phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathways in mouse endometrial stromal cells (ESCs; mESCs) and human ESCs. The function of nm23 in suppressing metastasis has been demonstrated in a variety of cancer types. nm23 also participates in the control of DNA replication and cell proliferation and differentiation. We first analyzed the expression profile of nm23 in mice during early pregnancy (n=6/group), pseudopregnancy (n=6/group) and artificial decidualization (n=6/group) and in humans during the menstrual cycle phases and the first trimester. We then used primary cultured mESCs and a human ESC line, T-HESC, to explore the hormonal regulation of nm23 and the roles of nm23 in in vitro decidualization, and as a possible mediator of downstream PI3K-Akt-mTOR signaling pathways. We evaluated the dynamic expression of nm23 in mice and humans using immunohistochemistry, western blot and real-time quantitative RT-PCR (RT-qPCR). Regulation of nm23 by steroid hormones was investigated in isolated primary mESCs and T-HESCs by western blot. The effect of nm23 knockdown (using siRNA) on ESC proliferation was analyzed by 5-ethynyl-2'-deoxyuridine staining (EdU) and proliferating cell nuclear antigen protein (PCNA) expression. The influence of nm23 expression on the differentiation of ESCs was determined by RT-qPCR using the mouse differentiation markers decidual/trophoblast PRL-related protein (dtprp, also named prl8a2) and prolactin family 3 subfamily c member 1 (prl3c1) and the human differentiation markers insulin-like growth factor binding protein 1 (IGFBP1) and prolactin (PRL). The effects of nm23 siRNA (si-nm23) and the PI3K inhibitor LY294002 on the downstream effects of nm23 on the PI3K-Akt-mTOR signaling pathway were estimated by western blot. NM23-M1 was specifically expressed in the decidual zone during early pregnancy and in artificially induced deciduoma, and NM23-H1 was strongly expressed in human first trimester decidua. The expression of nm23 was upregulated by oestradiol and progesterone (P<0.05 versus control) in vitro in mESCs and T-HESC, and this was inhibited by their respective receptor antagonists, ICI 182,780 and RU486. Mouse and human nm23 knockdown decreased ESC proliferation and differentiation (P<0.05 versus control). The PI3K-Akt-mTOR signaling pathways were downstream mediators of nm23 in mESCs and T-HESCs decidualization. Whether the nm23 regulates decidualization via the activation of AMPK, RAS, PKA, STAT3 or other signaling molecules remains to be determined. The role of nm23 in decidualization was tested in vitro only. Results demonstrate that nm23 plays a vital role in decidualization in mice and humans and that nm23 gene expression is hormonally regulated. The downregulation of nm23 in decidua during the first trimester may be associated with infertility in women. This study was supported by the National Natural Science Foundation of China (grant nos. 81370731, 31571551 and 31571190), the Science and Technology Project of Chongqing Education Committee (KJ130309), open funding by the Chongqing Institute for Family Planning (1201) and the Excellent Young Scholars of Chongqing Medical University (CQYQ201302). The authors have no conflicts of interest to declare.

Significance of TIMP-1 and nm-23 expressions in HER-2-positive breast cancer

Trastuzmab combined therapy has been recommended as standard therapy for HER-2-positive breast cancer. However, more than 70% HER-2-positive cases do not recur and might thus be with overtreatment risk. The aim of this study was to explore the significance of TIMP-1 and nm-23 expression in identifying the good prognosis subtype in HER-2-positive breast cancer. One hundred and sixty-five cases of HER-2-positive breast cancer treated in Tianjin Medical University Cancer Hospital from Jan. 1987 to Dec. 1988 were studied. Expressions of TIMP-1 and nm-23 were detected by immunohistochemistry and the correlation with clinicopathologic characteristics and long-term outcome was analyzed. 53.3% (88/165) of TIMP-1 and 72.7% (120/165) of nm-23 expression were detected in the patients. The TIMP-1-negative patients classified as good prognosis group had a 10-year metastasis free survival (MFS) of 58.4% and 10-year overall survival (OS) of 68.8%, compared with the 10-year MFS of 43.2% (P = 0.041) and 10-year OS of 52.0% in the positive group (P = 0.020). The nm-23-positive patients classified as good prognosis group had a 10-year MFS of 54.2% and 10-year OS of 65.7%, compared with the 10-year MFS of 40.0% (P = 0.049) and 44.1% (P = 0.015) in the negative group. The multivariate analysis showed that expressions of TIMP-1 and nm-23, tumor size and lymph node involvement were independent prognostic factors. In HER-2-positive breast cancer, TIMP-1 and nm-23 can be used to further distinguish between low-risk and high-risk subgroups, and they are independent factors in prognosis.

Association between underexpression of microrna-203 and clinicopathological significance in hepatocellular carcinoma tissues.

BackgroundAlthough recent studies have shown the utility of miR-203 as a cancer-relevant biomarker, the validated clinical significance of miR-203 in HCC remains obscure. The aim of the present study was to evaluate the relationship between miR-203 expression and clinicopathological features in HCC patients.MethodsMiR-203 expression in 95 formalin-fixed, paraffin embedded (FFPE) HCC tissues and their paired adjacent non-cancerous tissues was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Simultaneously, expression of miR-203 and its correlation with a variety of clinicopathological parameters and patient recurrence was analyzed.ResultsThe relative level of miR-203 was 1.1651 ± 0.70378 in HCC tissues, significantly lower than its expression in the corresponding adjacent non-cancerous liver tissues (2.2408 ± 0.75351, P < 0.001). The area under curve (AUC) of low miR-203 expression to diagnose HCC was 0.85 (95 % CI: 0.796 ~ 0.904, P = 0.027) at a cut-off value 1.99 evaluated by the median expression of miR-203 in all tissues, including HCC and normal liver tissues. Expression of miR-203 was negatively correlated to metastasis (r = −0.254, P = 0.013), clinical tumor nodes metastasis (TNM) stage (r = −0.300, P = 0.003), nm23 expression (r = −0.292, P = 0.004), p21 expression (r = −0.223, P = 0.030), microvessel density (MVD)(r = −0.206, P = 0.045) and was positively correlated to cirrhosis (r = 0.487, P < 0.001). Additionally, the recurrent time of lower miR-203 expression group was 57.949 ± 4.184 months, slightly longer than that in the high expression group (54.682 ± 2.591 months), however, no significant difference was noted (Chi-square = 0.206, P = 0.650).ConclusionsMiR-203 plays a vital role in the carcinogenesis and progression of HCC, which makes itself as a predictor for the deterioration of HCC. Furthermore, miR-203 may become a new target for molecular therapy in HCC.

Comparison of prognostic histopathological features in malignant melanoma with the expression of nm23 and p16 proteins

Comparison of prognostic histopathological features in malignant melanoma with the expression of nm23 and p16 proteins

Blockade of extracellular NM23 or its endothelial target slows breast cancer growth and metastasis.

Nucleoside Diphosphate Kinase (NDPK), described as NM23 a metastasis suppressor, is found in the culture medium of cancer cells lines suggesting that the kinase may have an extracellular role. We propose that extracellular NM23 released from breast cancers in vivo stimulates tumor cell migration, proliferation and endothelial cell angiogenesis in support of metastasis development. NM23 in the bloodstream of immunocompromised mice carrying human triple-negative breast cancers or in breast cancer patients was measured by ELISA. Primary and metastatic tumor development, the impact of blockade of NM23 and/or its stimulation of nucleotide receptors were measured using in vivo imaging. NM23 expression data in the Curtis breast dataset was examined to test our hypothesis that NM23 may play a mechanistic role in breast cancer development. SCID mice carrying metastatic MDA-MB-231Luc+ triple-negative human breast tumor cells elaborate NM23 into the circulation correlated with primary tumor growth. Treatment of mice with the NM23 inhibitor ellagic acid (EA) or the purinergic receptor antagonist MRS2179 slowed primary tumor growth. At 16 weeks following implantation, lung metastases were reduced in mice treated with EA, MRS2179 or the combination. Expression of NM23 in the Curtis breast dataset confirmed a likely role for NM23 in tumor metastasis. Extracellular NM23 may constitute both a biomarker and a therapeutic target in the management of breast cancer.

Loss of Nm23 is associated with a more favorable tumor microenvironment in patients with breast cancer.

Nm23 is a metastasis suppressor gene whose downregulation triggers metastatic progression. The aim of this study was to investigate the expression of Nm23 in breast carcinomas and its relationship with tumor microenvironment markers. A retrospective study was done (128 breast cancer patients from 2007 to 2010). Nm23, LPA1, SMA, CD34, CD8, and CD68 protein expressions were evaluated using immunohistochemistry. Image analysis was used to determine the immunostaining percentage area of Nm23, LPA1, and SMA; the number of the total vessel fraction CD34 positive; and the number of CD8+ and CD68+ cells. The mean ± SE was calculated. The differences among groups were evaluated using Student t-test for parametric data and Mann Whitney U test for nonparametric data. Cases were divided into two groups: Nm23+ and Nm23-. LPA1 immunostaining was significantly increased in Nm23- group. Immunostaining percentage area of SMA was not significantly higher when Nm23 was negative. CD34 immunopositive blood vessels, number of T CD8+ cells, and the number of macrophage CD68+ cells were increased when Nm23 was absent. Our results suggest that the absence of Nm23 causes an increase in LPA1, CD8+ and CD68+ inflammatory cells, and angiogenesis marker. Therefore, Nm23 loss could be associated with a more favorable environment for the development and dissemination of breast cancer. However, more studies are needed to determine this association.

A phase II study of medroxyprogesterone acetate in patients with hormone receptor negative metastatic breast cancer: translational breast cancer research consortium trial 007

Preclinical data suggest that medroxyprogesterone acetate (MPA) has both anti-metastatic and anti-angiogenic activity in the absence of hormone receptors (HR). This phase II trial assessed the activity of MPA alone or in combination with low-dose chemotherapy in patients with metastatic HR-negative breast cancer. Postmenopausal women with HR-negative disease were eligible if they had not received more than 3 chemotherapy regimens for metastatic disease. All patients were treated with MPA 1,000-1,500mg/day orally; patients in cohort two also received low-dose oral cyclophosphamide and methotrexate (ldCM, 50mg/day and 2.5mg twice daily on Days 1 and 2 each week). Tissue and circulating biomarkers were assessed serially. The primary endpoint was clinical benefit response defined as objective response or stable disease>6months. Thirty patients were enrolled (14 MPA monotherapy; 16 MPA+ldCM); median age was 55 (35-80); nearly all had visceral involvement. Despite dose escalation in 90% of patients, only 17 (57%) patients ever achieved MPA trough concentrations>50ng/ml. One patient developed grade 4 renal failure in the setting of rapid disease progression and dehydration. There were no objective responses. One patient in each cohort (~7%) had stable disease for>6months. Skin Nm23 expression increased after 4weeks of MPA+ldCM, but there were no significant changes in TSP-1, PAI-1 antigen, or PAI-1 activity. MPA had limited activity and does not warrant further development in patients with HR-negative advanced breast cancer. Poor bioavailability limited exposure despite dose escalation.

Correlation of Nm23 and P27 Expression in Nodal Diffuse Large B Cell Lymphomas with Clinicopathologic Parameters and the Effect on Prognosis

Objective: Diffuse large B cell lymphoma (DLBCL) is the most common type of adult lymphoma. No certain histopathological parameter was found, except proliferation index, for predicting prognosis. In hematological malignancies, the prognostic effect of Nm23 expression, which shows metastatic potential in solid tumors, has been researched by a few studies. Loss of p27, a negative regulator of the cell cycle, indicates aggressiveness; however, some studies showed that high expression is relevant to poor prognosis. Here, we aimed to investigate whether they can be used as prognostic markers in DLBCLs. Materials and Methods: Forty-two cases were included in the study. Demographic data were collected from hospital records. Manual immunohistochemical staining procedure was performed on one paraffin block of every case. Intensity and percentage of staining were grouped as positive and negative. Results: From 25 males and 17 female patients with a mean age of 62.9, 28 cases (66.7%) were Nm23-positive, and 13 (30.9%) were p27-positive. International Prognostic Index (IPI) score was relevant to prognosis. No significant relationship was found between prognosis and the expression of these two markers. Conclusion: Advanced age, high IPI score, and high serum lactate dehydrogenase (LDH) level were considered poor prognostic factors in DLBCLs. Larger series are needed for using Nm23 and p27 in predicting prognosis because of different results in the literature.

Significance of expression of p53 and nm23 in mucous adenocarcinoma of the rectum

Significance of expression of <i>p53</i> and <i>nm23</i> in mucous adenocarcinoma of the rectum

Clinical significance of expression of p85a, nm23 and MMP-2 in primary colorectal cancer and lymph node metastasis

Clinical significance of expression of p85a, nm23 and MMP-2 in primary colorectal cancer and lymph node metastasis

Significance of expression of p53, nm23 and Ki-67 in esophageal neuroendocrine carcinoma

目的：探讨p53、nm23和Ki-67在食管神经内分泌癌（neuroendocrine carcinoma,NEC）中的表达及其临床意义.方法：对42例NEC中p53、nm23及Ki-67的表达进行免疫组织化学检测.结果：NEC组织中p53的阳性表达率为97.62%,高表达为90.48%;nm23的阳性表达率为57.14%,高表达为33.33%;Ki-67阳性表达率为97.62%,高表达为61.90%.p53和Ki-67在NEC中高表达,与患者年龄、性别、部位、病理分类、浸润深度及淋巴结转移无关（P〉0.05）,nm23表达与患者年龄、性别、部位、病理分类无关（P〉0.05）,与浸润深度及淋巴结转移有关（P〈0.05）.结论：NEC具有不同于其他恶性肿瘤的生物学行为和免疫表型,患者预后差可能与p53和Ki-67的高表达有关,联合nm23检测,可为判断预后提供重要的依据.

Targeted Silencing of MART-1 Gene Expression by RNA Interference Enhances the Migration Ability of Uveal Melanoma Cells

Uveal melanoma (UM) is the most common primary intraocular malignancy and the leading potentially fatal primary intraocular disease in adults. Melanoma antigen recognized by T-cells (MART-1) has been studied extensively as a clinically important diagnostic marker for melanoma, however, its biological function remains unclear. In the present study, the UM cell line SP6.5, which showed a high level of MART-1 expression, was subjected to small interfering RNA-mediated silencing of MART-1. Silencing of MART-1 expression increased the migration ability of SP6.5 cells and down-regulated the expression of the metastasis suppressor NM23. Our results suggest that MART-1 is a candidate target for the development of therapeutic strategies for UM and in particular for the suppression of metastasis associated with this malignancy.

Immunohistochemical expression and significance of NM23 suppressor protein in primary gastric adenocarcinoma

NM 23 protein was originally identified as a metastasis suppressor protein. The expression of NM23 has been correlated with tumour metastatic potential in various human carcinoma, mostly in ductal breast and colorectal carcinomas. Evidence for their expression in gastric cancer is rather contradictory, both for protein expression status and prognostic value. This study was done to analyze the immunohistochemical expression of NM23 in gastric carcinoma, and correlation of the degree of staining with clinicopathological parameters was investigated. In a retrospective immunohistochemical study specimens obtained from 56 gastric cancer patients who had undergone gastrectomy with perigastric lymphadenectomy were analysed, in correlation with classical clinical-pathological parameters of tumours, WHO-, Lauren-, Goseki-, and Ming- classification. NM 23 gene expression was compared in gastric adenocarcinoma and tumour-adjacent non-neoplastic gastric mucosa. A semiquantitative immunostaining evaluation (score 0-3) was used, counting the percentage of stained cells. Statistical analysis was performed using Kolmogorov-Smirnov test, and Spearman rank correlation test. The investigated group consisted of 40 males and 16 females (2.5:1) with a mean age of 63 years (range: 48-81 years). The percentage of positive expression of NM23 (score 3) were in 30 (53.5%) specimens in non-neoplastic mucosa in adjacent gastric carcinoma, and negative (score 0-2) in all 56 (100%) specimens of gastric adenocarcinoma. NM23 expression was higher in non-neoplastic mucosa than in adjacent gastric adenocarcinoma tissue (p<0.0001). NM23 protein expression did not correlate with gender (p=0.115), tumour size (p=0.844), tumour grade (p=0.172), lymphovascular invasion (p=0.606), lymph node metastases (p=0.311), Lauren classification (p=0.426), Goseki classification (p=0.458) and Ming classification (p=0.212). Our series did not show a significant correlation between NM23 expression and analysed clinico-pathological variables, but these results suggest that protein NM23 may have a role in gastric carcinoma pathogenesis.

The expression of BRCA1, P53, KAI1, and Nm23 in ovaries of BRCA1 mutation carriers after prophylactic adnexectomy

IntroductionHigh mortality rate, absence of reliable methods for early diagnosis and poor prognosis of advanced ovarian cancer prompted to investigate the role of prophylactic oophorectomy in BRCA1 mutation carriers as well as evaluate the expression of BRCA1, p53, Nm23, and KAI1 proteins in ovarian tissue from these patients.Materials and methodsOvaries from BRCA1 mutation carriers underwent prophylactic adnexectomy and control group of patients were operated from other than cancer reasons. The expression of selected proteins was studied using immunohistochemical staining. The intensity of immunostaining and the number of tumor cells showing the reaction for selected proteins were analyzed.ResultsWe have analyzed ovarian tissues from 18 BRCA1 mutation carriers and 11 women included in control group. Positive expression of BRCA1 protein was presented in 83.3 % cases in BRCA1 mutation carriers and in 72.7 % in the control group (p > 0.05). Positive expression of p53 protein was observed, respectively, in 27.8 vs. 36.4 % (p > 0.05), Nm23 protein 77.7 vs. 90.9 % (p > 0.05), and KAI1 in 72.2 vs. 72.7 % (p > 0.05). Mean percent of tumor cells that showed the reaction for selected proteins as well as the intensity of immunostaining for all analyzed proteins seems to be lower in BRCA1 mutation carriers.ConclusionsHowever, any significant differences between study group and control group have not been found; there were similar trends showing reduced expression of studied proteins in BRCA1 mutation carriers.

HMSH2 and nm23 Expression in Sporadic Colorectal Cancer and its Clinical Significance

To study the expression of the mismatch repair proteins hMSH2 and nm23 in sporadic colorectal cancer, determine any inter-relationship, and further investigate any clinical significance. Expression of hMSH2 and nm23 proteins was assessed in 87 colorectal cancer tissues by SP immunohistochemistry, with analysis of survival using follow-up data. In the sporadic colorectal cancer tissues, nm23 protein expression appeared independent of the histological type (P > 0.05), but correlated with the invasion depth and lymphatic metastasis (P < 0.05). In contrast, hMSH2 protein expression was not significantly correlated with these clinicopathologic features (P > 0.05), although it positively correlated with that of nm23 protein in the sporadic colorectal cancers (rs=0.635, P < 0.05). Combined expression of the two was found to be related with invasion depth, lymphatic metastasis and prognosis of sporadic colorectal cancer (P < 0.05). nm23 protein level was related with the degree of malignancy, and could be used as an index to predict the invasion and metastasis potential. The expression of hMSH2 protein is positively correlated that of nm23 protein, and the combined expression of the two has certain guiding significance for the prognosis of sporadic colorectal cancer.