nm23-H1 Gene Research Articles

Nm23-H1 reduces in vitro cell migration and the liver metastatic potential of colon cancer cells by regulating myosin light chain phosphorylation.

The nm23-H1 gene is known as a potential metastasis suppressor gene in various types of carcinomas. However, the role of nm23-H1 in colorectal carcinoma still remains controversial and the cellular mechanisms by which its protein may modulate the metastatic phenotype are not yet known. We transfected nm23-H1 cDNA into the human colon cancer cell line, HT-29, to test the effects and cellular biological mechanism of nm23 protein in colon cancer. We found that nm23-H1 strongly inhibited the liver metastasis of HT-29 cells in nude mice and inhibited the epidermal growth factor (EGF)-induced cell migration in vitro. Furthermore, we clarified the regulation of the myosin light chain (MLC) phosphorylation by nm23-H1, which has been demonstrated as having potential role in cell migration.

579 Significant tumor growth inhibition of glioblastoma xenografts by NNC 47-0011 — a low molecular weight tricyclic tyrosine kinase modulator with anti-angiogenic activity

Pemetrexed disodium (Alimta®), LY231514, is an antifolate that is able to simultaneously inhibit the synthesis of purines and pyrimidines. Pemetrexed has been approved for first- and second-line treatment in patients with non-small cell lung cancer (NSCLC). However, there is still a lack of clinical biomarkers for predicting the therapeutic response to pemetrexed. The aim of this study is to establish new biomarkers for pemetrexed treatment in NSCLC.Human NSCLC cell lines were exposed to pemetrexed. The antitumor effect was measured by growth inhibition with MTT assay and expression of cell cycle mediators with immunoblots. Using the Superarray cancer pathway gene array, 482 genes were screened for differential expression in A549 cells that were untreated or treated with pemetrexed.A549 cells exhibited sensitivity but H1355 cells showed resistance to pemetrexed. To investigate the mechanisms of responsiveness and nonresponsiveness to pemetrexed in these cell lines, we measured the expression levels of thymidylate synthase (TS), dihydrofolate reductase (DHFR), reduced folate carrier, and folylpoly-gamma-glutamate synthetase genes. TS, DHFR, and reduced folate carrier gene expressions were significantly reduced in A549 and H1355 cells. Pemetrexed caused cell cycle arrest in the G1 phase and S phase in H1355 and A549 cells, respectively. Significantly higher expressions of many genes, especially lipocalin-2 (Lcn-2) and nm23-H1 proteins, were noted in A549 cells treated with pemetrexed in comparison with untreated cells. Furthermore, reverse transcriptase polymerase chain reaction and Western blot showed that Lcn-2 and nm23-H1 expressions increase in response to pemetrexed treatment in a dose-responsive manner in pemetrexed-sensitive A549 cells but not in resistant H1355 cells.Our results indicated that downregulation of TS and DHFR genes and upregulation of p21, p27, Lcn-2, and nm23-H1 genes may serve as new biomarkers for predicting responsiveness to pemetrexed.

Expression of PCNA and nm23-H1/NDPK in Hepatocellular Carcinoma following transcatheter arterial chemoembolization therapy

AIM:To study the effect of transcatheter arterial Chemoembolization (TACE) on the proliferation and metastasis of the hepatocellular carcinoma (HCC). METHODS:Seventy-two patients with inoperable huge HCC administered from 1992 to 2000 were treated with TACE initially, and then operated following the shrinkage of the tumor. During same periods of treatment, there were comparable 487 HCC patients who were not treated with TACE, of which 32 pairs of patients who met with the criteria were selected for this study based on the 10 items screening criteria including gender, age, history of the disease, BUS examination. Expression of proliferating of cell nuclear antigen (PCNA) and nm23-H1 were studied by immunohistochemistry. RESULTS:PCNA label index (PCNA LI) of HCC following TACE was elevated. The distribution of PCNA LI in the range 25 %, 26-50 %, 51-75 % and 75 % is 75 %, 14.3 %, 10.7 % and 0 % in control group, and 35.7 %, 21.4 %, 28.6 % and 14.3 %, in TACE group (P <0.01, n =28), respectively. The expression of nm23-H1 gene exists in both cytoplasm and nuclear with no significant difference between treatment and control group. CONCLUSION:The proliferative activity of residual tumor of HCC following TACE causes the elevation of PCNA LI implying the poor prognosis of long-term effect of TACE, and therefore, it is necessary to perform two stage-resection after TACE of HCC.

P53 is a regulator of the metastasis suppressor gene Nm23-H1.

p53, a tumor suppressor gene involved in the G1 cell cycle checkpoint, is also the most frequently mutated gene in human cancer. In addition, p53 modifies the ability of tumor cells to metastasize. The metastasis-associated gene Nm23-H1, which encodes an 18-kDa nucleoside diphosphate kinase, was previously identified in cells with low metastatic potential. Although p53 and Nm23-H1 proteins play an important part in regulating the progression of cancer, any functional relationship between these two proteins is currently unknown. Here we report an association between p53 levels and expression of the Nm23-H1 gene. Our data indicate that wild-type (wt) p53 upregulated the expression of Nm23-H1 at protein and mRNA levels in MCF-7 and J7B cells. This capacity of wt p53 to regulate expression of Nm23-H1 was not only dependent on the endogenous but also the exogenous origin of p53, and could not be reproduced with mutant p53. Subsequently, the invasive ability of MCF-7 and J7B cells was suppressed upon induction of the Nm23-H1 protein by p53. In contrast, increased levels of p53 downregulated the expression of Nm23-H1 at the protein and mRNA levels in RKO and H1299 cells and, as a consequence, increased the invasive ability of both cell types. Thus, our results implicated the differential regulation of Nm23-H1 by p53 in different cell types as an important component in the molecular mechanisms of tumor metastasis.

Relationship between expression of nm23H1 gene and in vivo and in vitro invasive capacity of gastric cancer cells

Relationship between expression of nm23H1 gene and <i>in vivo</i> and <i>in vitro</i> invasive capacity of gastric cancer cells

Prediction of lymph node metastasis based on p53 and nm23-H1 expression in muscle invasive grade III transitional cell carcinoma of bladder.

A surgically positive lymph node in invasive bladder cancer generally implies distant micrometastasis; thus, preoperative identification of lymph node status is important. Various antioncoproteins were evaluated for their accuracy in predicting lymph node metastasis. Fifty-seven subjects who had invasive, grade III transitional cell carcinoma at TURB, and then were confirmed to have stage T2, T3a, and T3b tumors after radical cystectomy from 1985 to 1994, were selected. Tissues acquired from transurethral resection were immunostained with tumor suppressor gene p53 (DO7 and PAb 1801) and antimetastatic gene nm23-H1 (NM301). Results of staining and pathological staging were compared with the status of lymph node metastasis. Expression of p53 was 42.1% (24/57) for DO7 and 22.8% (13/57) for PAb1801, with DO7 exhibiting superiority over PAb1801. Expression of nm23-H1 was seen in 50.9% (29/57) of cases. Combined analysis of p53 and nm23-H1 expression and nodal status (N stage) was not significant. However, pathological nodal status was statistically significantly correlated with pathological tumor (T) stage and p53 expression. A high risk of lymph node metastasis can be predicted when Grade III, muscle invasive tumor and p53 expression are seen from TURB specimens. Lymph node metastasis is correlated with the degree of invasion in Grade III muscle invasive tumors--especially in T3b tumors, where there is highest probability of node involvement.

Expression and clinical significance of nm23-H1 and CD44v6 in non-small cell lung cancer

To study the role of nm23-H1 and CD44v6 gene in non-small cell lung cancer (NSCLC). Expressions of nm23-H1 and CD44v6 genes were analyzed in 147 cases of NSCLC by SP immunohistochemistry method. The overall positive rate of nm23-H1 staining was 62.6% (92/147). Significant differences in the positive rate of nm23-H1 were found between well and poor differentiated groups [68.6% (83/121) [WTBX]vs 34.6% (9/26)], and between adenocarcinoma and squamous cell carcinoma , and between adenocarcinoma and squamous cell carcinoma [78.8% (52/66) [WTBX]vs 50.8% (32/63) ] ( (P < 0.05), but not between stage I+II and stage III+IV [ 65.3% (62/95) [WTBX]vs 57.7% (30/52) ], and between N0 and N1-3 , and between N0 and N1 3 [64.7% (55/85) [WTBX]vs 59.7% (37/62) ]( ( P > 0.05). The positive rate of nm23-H1 of patients who survived for more than 3 years was 71.4% (55/77), which was significantly higher than 52.9% (37/70) of patients who survived for less than 3 years (Chi-square=5.4, P < 0.05). For CD44v6, the overall positive rate was 63.9% (94/147). Significant differences in the positive rate of CD44v6 were found between well and poor differentiated groups [68.6% (83/121) [WTBX]vs 42.3% (11/26)], and between adenocarcinoma and squamous cell carcinoma , and between adenocarcinoma and squamous cell carcinoma [53.0% (35/66) [WTBX]vs 77.8% (49/63) ] ( (P < 0.05), but not between stage I+II and stage III+IV [ 66.3% (63/95) [WTBX]vs 59.6% (31/52) ], and between N0 and N1-3 , and between N0 and N1 3 [63.5% (54/85) [WTBX]vs 64.5% (40/62) ]((P > 0.05). The positive rate of CD44v6 of patients who survived for more than 3 years was much lower than that of patients who survived for less than 3 years (43/74 vs 51/70, P < 0.01 ). The 3-year survival rate in patients with nm23-H1(+)CD4v6(-) was significantly higher than those with nm23-H1(-)CV44v6(+) (22/32 vs 11/34, P < 0.01). There are some relationships among expressions of nm23-H1 and CD44v6 in NSCLC and cell differentiation, histological classification and prognosis, and no relation in stage and lymph node metastasis.

Characterization of the nm23-M2, nm23-M3 and nm23-M4 mouse genes: comparison with their human orthologs

The nm23 gene family is thought to be involved in physiopathological processes such as growth, differentiation and cancer promotion, progression or metastasis. We report here the mouse nm23-M3 and nm23-M4 complementary DNA sequences and the genomic cloning, characterization and tissue expression pattern of the nm23-M2, nm23-M3 and nm23-M4 genes, in comparison with their human and rat orthologs and with the human nm23-H1 and mouse nm23-M1 genes. The organization and structure of the members of this gene family are remarkably similar in human and rodents. Accordingly, the striking similarities between the human and mouse nm23 genes enable the use of mouse transgenic and knock-out models for studying the role of nucleoside diphosphate kinase isoforms in human physiopathology.

The N-myc and c-myc downstream pathways include the chromosome 17q genes nm23-H1 and nm23-H2.

Gain of chromosome 17q material is the most frequent genetic abnormality in neuroblastomas. The common region of gain is at least 375 cR large, which has precluded the identification of genes with a role in neuroblastoma pathogenesis. Neuroblastoma also frequently show amplification of the N-myc oncogene, which correlates closely with 17q gain. Both events are strong predictors of unfavorable prognosis. To identify genes that are part of the N-myc downstream pathway, we constructed SAGE libraries of an N-myc transfected and a control cell line. This identified the chromosome 17q genes nm23-H1 and nm23-H2 as being 6-10 times induced in the N-myc expressing cells. Northern and Western blot analysis confirmed this up-regulation. Time-course experiment shows that both genes are induced within 4 h after N-myc is switched on. Furthermore, we demonstrate also that c-myc can up-regulate nm23-H1 and nm23-H2 expression. Neuroblastoma tumor and cell line panels reveal a striking correlation between N-myc amplification and mRNA and protein expression of both nm23 genes. We show that the nm23 genes are located at the edge of the common region of chromosome 17q gain previously described in neuroblastoma cell lines. Our findings suggest that nm23-H1 and nm23-H2 expression is increased by 17q gain in neuroblastoma and can be further up-regulated by myc overexpression. These observations suggest a major role for nm23-H1 and nm23-H2 in tumorigenesis of unfavorable neuroblastomas.

Activation of antimetastatic Nm23-H1 gene expression by estrogen and its alpha-receptor.

Metastasis of various malignant cells is inversely related to the abundance of the Nm23-H1 protein. The role of estrogens in tumor metastasis has now been investigated by examining the effect of E2 on the expression of the Nm23-H1 gene. Three human breast carcinoma cell lines, in which endogenous ERalpha is expressed at different levels, were used as a tool to assess the role of ERalpha in Nm23-H1 gene-mediated metastasis. E2 induced time-dependent increases in the abundance of Nm23-H1 mRNA and protein, with the extent of these effects correlating with the level of expression of ERalpha. E2 induced a marked decrease in the invasive activity of MCF-7 and BT-474 cells but had no effect on BCM-1 cells, which had virtually no ERalpha. Consistent with these results, the ER-mediated Nm23-H1 promoter activity was inhibited 3-fold by the E2 antagonist, ICI 182,780. Deletion analysis of the promoter region of the Nm23-H1 gene identified a positive estrogen-responsive element located in -108/-94. ER protein bound specifically to the -108/-79 fragment with high avidity. These results indicate that E2, acting through ERalpha, activated transcription of the Nm23-H1 gene via a positive estrogen-responsive element in the promoter region of the gene. These results suggest that E2 could suppress tumor metastasis by activating the expression of the Nm23-H1 gene.

Activation of Antimetastatic Nm23-H1 Gene Expression by Estrogen and Its -Receptor

Activation of Antimetastatic Nm23-H1 Gene Expression by Estrogen and Its -Receptor

Transfection of the nm23-H1 gene into human hepatocarcinoma cell line inhibits the expression of sialyl Lewis X, alpha1,3 fucosyltransferase VII, and metastatic potential.

The expressions of Lewis antigens, alpha1,3 fucosyltransferase (alpha1,3 FucT)-VII, and the metastatic potential of the 7721 human hepatocarcinoma cell line after the transfection of the cDNA of nm23-H1, a known metastasis-suppressive gene, were studied using mock cells as the control, which were transfected with the pcDNA3 vectors. Cell adhesion to human umbilical vein epithelial cells (HUVEC), chemotaxic cell migration through transwells, and invasion through matrigel were selected as the metastasis-related phenotypes to assess the metastatic potential at the cell level. The results showed that the expression of SLe(x) was high, while the expression of Le(x), SDLe(x), and SLe(a) were very low on the surface of the mock cells. After transfection of nm23-H1, the expressions of SLe(x), alpha1,3 FucT-VII, and the cell adhesion to HUVEC, as well as cell migration and invasion were simultaneously decreased in all three clones of nm23-H1-transfected cells. Among different clones, the decreased expressions of SLe(x) and alpha1,3 FucT-VII were roughly correlated to each other, and also, in general, proportional to the ability of cell adhesion to HUVEC, cell migration, and invasion. The expressions of these metastasis-related phenotypes were lowest in clone 3 and highest in clone 4. Only the specific monoclonal antibody to SLe(x) (KM93) significantly abolished the cell adhesion, migration, and invasion, while other monoclonal antibodies against SDLe(x) or Le(x) and SLe(a) only slightly inhibited or entirely failed to inhibit the above-mentioned phenotypes. However, the rate of cell growth was not changed after the transfection of nm23-H1, and the ability of colony formation on the soft agar was only decreased in one clone. These findings reveal that the down-regulation of alpha1,3 FucT-VII and its product, SLe(x), is one of the mechanisms to explain the metastasis-suppressive effect of the nm23-H1 gene.

Expression and localization of nm23-H1 in the human placenta.

The involvement of the nm23 gene, initially documented as a putative metastasis-suppressor gene, in normal development and differentiation has been supported by several investigations. To date, however, localization and expression pattern of nm23 in the human placenta has not been determined. In the present study, the expression of nm23-H1 was examined by Northern blot and immunohistochemical analyses in human placentas from various stages of gestation. In first trimester placenta, the villous cytotrophoblast and the extravillous trophoblast exhibited strong cytoplasmic staining for nm23-H1. In second trimester and term placentas, the few cytotrophoblasts present showed less intense staining than those in first trimester placenta. Northern blot analysis demonstrated a progressive decrease in nm23-H1 gene expression with advancing gestational age, which is consistent with the results obtained by immunohistochemistry. These findings suggest that nm23-H1 is involved in the differentiation process of the trophoblast, and high levels of nm23-H1 expression seem to reflect the proliferating, less differentiated state of that reserve.

The significance of nm23 gene expression in embryonic tissues and lung cancer tissues

To clarify the relationship between nm23-H1 gene and differentiation of embryonic tissues and the significance of its expression in pulmonary carcinoma. nm23-H1 protein ( NM23-H1) was detected in the embryonic tissues of SD rats and human being, as well as in human lung cancer tissues, by immunohistochemistry method. Only embryonic tissues with definite configuration ( organ structure) expressed NM23-H1 constantly. Positive rate of NM23-H1 was 34. 7% in 49 cases of human lung cancer tissues, and 27. 3% in squamous cell carcinoma, 50. 0% in adenocarcinoma. The positive rate of NM23-H1 was 22. 2% in 27 cases of hilar lymph node metastatic foci, and 34. 8% in primary tumour foci ( P > 0. 05) . There was no significant difference of lymphatic metastatic rates between NM23-H1 positive and negative primary tumors. There is positive correlation between accumulation of NM23-H1 and differentiation of embryonic tissues and lung carcinoma. NM23-H1 may play an important role in maintaining a stable epithelial structure. It doesn't show that NM23-H1 can directly inhibit the metastasis of lung cancer cells.

Nm23-H1 gene as a molecular switch between the free-floating and adherent states of gastric cancer cells

The contribution of the nm23-H1 gene to metastasis in malignant tumors, including gastric cancer, is controversial. In this study, we compared nm23-H1 levels in two cell subtypes with different morphologies (floating and adherent states), but that were derived from the same gastric cancer cell line, KATO-III. A real-time quantitative reverse transcription-polymerase chain reaction showed that the number of nm23-H1 mRNA molecules in floating cells was significantly higher than that in adherent cells ( P<0.0001). The average of the copies in floating cells was approximately 2.4-fold higher than that in adherent cells. Consistent with mRNA levels, intracellular levels of nm23-H1 protein were higher in floating cells than in adherent cells. There was no difference in cell cycle characteristics between the two subtypes. In conclusion, our present data indicate that expression of nm23-H1 by a tumor could be altered during the different steps in metastases, suggesting that nm23-H1 may act as a molecular switch between the free-floating and adherent states of cancer cells.

Expression of p16, nm23-H1, E-cadherin, and CD44 gene products and their significance in nasopharyngeal carcinoma.

The present study was aimed to determine whether p16/MTS1, nm23-H1, E-cadherin, and CD44 proteins were expressed in nasopharyngeal carcinoma (NPC) and whether those expressions were pathologically significant in the progress of NPC. We examined non-cancerous nasopharyngeal mucosa (20 cases) and NPC (80 cases) using immunohistochemistry with six different types of monoclonal antibodies against p16, nm23-H1, E-cadherin, CD44H, CD44v3, and CD44v6 proteins. The results showed that 1) the rates of positive p16 protein expression and of preserved E-cadherin protein expression in NPC were significantly lower than those in non-cancerous tissue (P <.01); 2) no significant difference in the rate of positive expression of nm23-H1, CD44H, CD44v3, and CD44v6 proteins were observed between non-cancerous nasopharyngeal mucosa and NPC; 3) no significant difference in the expression of those proteins were found by respective correlation analyses of sex, stage, and size of primary tumor in NPC; and 4) no significant difference in the rates of positive expression of CD44H, CD44v3, and CD44v6 proteins were observed in NPC between with and without lymph node metastasis, indicating that those gene products did not correlate with lymph node metastasis in NPC. However, there were inverse correlations between the expression of p16, nm23-H1, or E-cadherin protein and lymph node metastasis (P <.05), indicating that the expression of p16, nm23-H1, and E-cadherin gene were related to the carcinogenesis and tumor progression of NPC. Detecting the expressions of those gene products may provide clinically valuable information for therapeutic strategy and for predicting the prognosis of patients with NPC.

Expression of nm23-H1 gene product in mediastinal lymph nodes from lung cancer patients.

Although numerous studies have shown that nm23-H1 gene product expression is inversely related to metastatic potential in some cancers, the expression in lymph nodes has not been studied in detail. An analysis of nm23-H1 gene product expression in mediastinal lymph nodes from lung cancer patients is reported. One hundred and thirty-four, randomly selected lymph nodes (63 with positive pathological lymph node status) from 39 surgically treated lung cancer patients were examined. Expression of nm23-H1 gene product was determined using specific monoclonal antibodies. Metastatic cancer cells were highlighted using anti-cytokeratin antibody. Expression of nm23-H1 gene product in patients with less and more than 50% nodes-positive was 12/23 (52.2%) and 15/16 (93.8%) cases, respectively. Immunohistochemical studies with cytokeratin revealed micrometastasis in 6/39 (15.4%) patients and 9/71 (12.7%) nodes previously reported as cancer negative. Expression of nm23-H1 gene product in micrometastasis and metastasis-positive nodes was 5/9 (55.6%) and 55/63 (87.3%), respectively. We also found nm23-H1 gene product expression in germinal center cells. However, we found no relationship between expression of nm23-H1 gene product in germinal center cells and extent of metastasis. Our study demonstrates a positive relationship between expression of nm23-H1 gene product and extent of metastasis in mediastinal lymph nodes from lung cancer patients. Our data for normal germinal center cells suggests that nm23-H1 gene product expression does not play a specific biological role in suppressing tumor metastasis in lung cancer.

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

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. 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. 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. 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.

Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival.

BackgroundWe assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma.MethodsFormalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody.ResultsExpression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87).ConclusionsIn patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion.

Reappraisal of the role of NM23-H1 in colorectal cancers.

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. 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. 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. The results indicate that nm23-H1 gene does not play an important part in the progression of colorectal carcinogenesis.