OBJECTIVETo investigate the relationship between expression of cell adhesion molecular CD44, epithelial cadherin (E-cad) and metastatic suppressor gene nm23-H1 as well as the clinicopathologic features including cell differentiation, invasion and metastasis of thyroid follicular-derived carcinoma.

METHODSForty two (42) thyroid follicular carcinomas (FTC) and 54 papillary carcinomas (PTC) were collected for studying the expression of CD44, E-cad and nm23-H1 using immunohistochemical staining.

RESULTSNeoplastic epithelium and infiltrating lymphocyte expressed CD44 in an intense plasma membrane pattern. CD44 expression rates in poorly differentiated FTC (80%) and PTC cases with metastasis (78%) were significantly higher than those of well-differentiated FTC cases (64%) and PTC without metastasis cases (59%) respectively. Thyroid carcinoma tissue was positive for E-cad and nm23-H1 in a cytoplasm pattern. Well-differentiated FTC presented a higher E-cad and nm23-H1 expression rate than poorly-differentiated FTC, but both had a lower expression rate than that of PTC (70% and 76%, P < 0.01). The expression rate and intensity of E-cad and nm23-H1 were lower and less in metastatic PTC than those in primary PTC. Expression rate of CD44 (72%) in thyroid follicular-derived carcinoma was higher than those of E-cad (54%, P < 0.01) and nm23-H1 (61%, P < 0.05). E-cad expression was adversely correlated with that of nm23-H1 (chi(2) = 15.75, P < 0.011, r = 0.522 2). There was a reverse relationship between expression of CD44 and E-cad or nm23 (P > 0.05).

CONCLUSIONSCell differentiation degree in FTC and metastasis in PTC have positive correlation with the expression of E-cad and nm23, but have a reverse correlation with the expression of CD44. There was a relationship between expression of CD44, E-cad, nm23 and the characteristics of the degree of differentiation, metastatic potential and the prognosis of thyroid follicular-derived carcinoma.

Adult ; Aged ; Cadherins ; analysis ; Carcinoma, Papillary, Follicular ; chemistry ; pathology ; Female ; Humans ; Hyaluronan Receptors ; analysis ; Immunohistochemistry ; Male ; Middle Aged ; Monomeric GTP-Binding Proteins ; analysis ; NM23 Nucleoside Diphosphate Kinases ; Neoplasm Invasiveness ; Nucleoside-Diphosphate Kinase ; Thyroid Neoplasms ; chemistry ; pathology ; Transcription Factors ; analysis

OBJECTIVETo assess the significance of expression of sialylated carbohydrate antigens and nm23-H1 gene in metastasis and prognosis of breast cancer.

METHODSTissue specimens from 102 cases of primary breast cancer were stained with antibodies against sialyl Lewis A (SleA) and salyl Lewis X (SleX), and nm23-H1 proteins by immunohistochemical methods.

RESULTOf the 102 cases, the positive cases of SleA and SleX were 24.5% (25/102) and 59.89% (61/102),respectively; the reduced expression of nm23-H1 was showed in 37.3% (38/102) of the cases. The positive expression of SleX and the reduced expression of nm23-H1 gene were significantly associated with lymph node involvement. Among the 100 patients who underwent curative surgery, the disease-free survival rate was significantly correlated with nm23-H1 and SleX expression, respectively,but not with SleA expression. In multivariate analysis using Cox regression model, combination assay of nm23 H1 and SleX expression emerged as independent prognostic factors.

CONCLUSIONThese results suggest that nm23-H1 gene and SleX may be involved in the metastatic process in human breast cancer, and immunohistochemical detection of SleX and nm23-H1 may be used as a biologic marker of prognosis.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; chemistry ; genetics ; mortality ; Female ; Gangliosides ; analysis ; Humans ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; genetics ; Oligosaccharides ; analysis ; Prognosis ; Survival Rate

OBJECTIVETo identify molecular markers of lung squamous cell carcinoma by cDNA microarray technique.

METHODScDNA expression profiles were examined by microarrays of 6 surgical specimens of stage I lung squamous cell carcinomas. Those genes, either up-regulated or down-regulated in every specimen studied, were identified. The expression levels of nm23 and BRCA2 by the squamous cell carcinoma of the lung were further examined by immunohistochemical techniques.

RESULTSA total of 107 genes were identified, of which 26 were up-regulated and 81 were down-regulated in all six specimens. Immunohistochemical staining showed that, compared with normal lung tissues, the intensity of nm23 expression by the squamous cell carcinoma of lung was significantly increased while that of BRCA-2 was decreased.

CONCLUSIONcDNA microarrays can be used to identify gene expression profile of lung cancer, some of which may be used as markers of lung squamous cell carcinoma.

BRCA2 Protein ; metabolism ; Biomarkers, Tumor ; Carcinoma, Squamous Cell ; genetics ; metabolism ; Gene Expression Profiling ; Humans ; Lung Neoplasms ; genetics ; metabolism ; Male ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; metabolism ; Oligonucleotide Array Sequence Analysis

OBJECTIVETo study the effect of nm23-h1 transfection on proliferation characteristics of adnoid carcinoma cell lines in vitro and in vivo.

METHODSIn vitro ACC-M cell lines were incubated after putative anti-metastatic gene nm23-h1 was introduced into the cells with the help of G418 selective incubation base. The ACC-M cells were transplanted into 10 BALB/C nude mices subcutaneously and non-transfected cell lines were taken as control. Immunohisto chemistry and Ki67 antibody were employed to study the proliferation character of cell crawling pieces and paraffin-bedded slice, meanwhile, the solid tumor of both groups were prepared for flow cytometry(FCM).

RESULTSTransfected cells grew slower than non-transfected cells and this trend became more obvious as passages passed on. In vitro the expression of Ki67 of transfected cells was little stronger than non-transfected cells, while the expression of Ki67 in solid slices was almost negative in both groups. Transfected cells presented slower growth than non-transfected cells in the early stage (2 weeks) and 2 weeks later there was no obvious difference in size(P > 0.05). FCM value accorded well with the result.

CONCLUSIONIntroduction of nm23-h1 into the ACC-M cell lines may have transient inhibitory effects on its proliferation.

Animals ; Antibodies ; analysis ; Carcinoma, Adenoid Cystic ; genetics ; pathology ; Cell Division ; Cell Line, Tumor ; Female ; Genetic Therapy ; Ki-67 Antigen ; immunology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mouth Neoplasms ; genetics ; pathology ; NM23 Nucleoside Diphosphate Kinases ; Neoplasm Transplantation ; Nucleoside-Diphosphate Kinase ; Proteins ; genetics ; Transfection

Expression of nucleoside diphosphate(NDP) kinase, which is homologous to the nm23 gene product in a variety of species, has been found to be inversely associated with metastatic potential. However, the relationship remains controversial according to the tumor cell types and experimental system, with conflicting results from different research groups. In order to determine whether NDP kinase expression serves as a marker for metastatic potential in human skin cancer, we assessed the levels of NDP kinase expression in 9 keratoacanthomas (KAs), 26 squamous cell carcinomas (SCCs), and 25 basal cell carcinomas (BCCs) using immunohistochemistry. The expression of NDP kinase was intense in KA and SCC compared with BCC. However, the difference of NDP kinase expression between KA and SCC was not statistically significant. And there was no statistically significant difference in NDP kinase expression between SCC with metastasis and SCC without metastasis. Our results contradict the hypothesis concerning the possible role of nm23 gene as a metastatic suppressor gene in human skin cancer. The mechanism of overexpression in various tumor cell types and its biological significance in cutaneous carcinogenesis remain to be determined.
Antibodies, Monoclonal ; Carcinoma, Basal Cell/enzymology/secondary ; Carcinoma, Squamous Cell/enzymology/secondary ; Comparative Study ; Erythrocytes/enzymology ; Human ; Immunohistochemistry ; Keratoacanthoma/enzymology ; Nucleoside-Diphosphate Kinase/*analysis/blood ; Skin Diseases/enzymology ; Skin Neoplasms/*enzymology/secondary ; Transcription Factors/analysis

To identify the clinicopathological events including nm23 expression that underlies progression in renal cell carcinoma, a retrospective analysis of patients with renal cell carcinoma was performed. Ninety-eight cases of radical nephrectomies with extensive regional or para-aortic lymph node dissection were assessed for clinicopathological variables, and eighty-five cases underwent nm23/NDPK-A protein immunohistochemical staining. Significant parameters in survival were tumor size, histologic pattern, Fuhrman's nuclear grade, pathologic T(pT) stage, pathologic N stage, M stage, tumor thrombi, location of metastasis, and nm23 staining intensity. To assess the relationship with survival, the tumors with low and high nm23 expressions were compared. The fifty-nine patients with a high staining intensity had a significantly worse survival than did the twenty-six with a low staining intensity (p = 0.0015). Additionally nm23 staining intensity was correlated with tumor size, Fuhrman's nuclear grade, pT, and distant metastasis. Therefore, the immunostaining intensity of nm23 protein could be used as a prognostic parameter with an inverse correlation.
Adult ; Aged ; Carcinoma, Renal Cell/*enzymology/mortality/pathology ; Disease-Free Survival ; Female ; Human ; Kidney Neoplasms/*enzymology/mortality/pathology ; Male ; Middle Age ; Neoplasm Staging ; Nucleoside-Diphosphate Kinase/*analysis ; Prognosis ; Transcription Factors/*analysis

To evaluate the role of p53 and NDP-K/nm23(nm23) protein as a prognostic factor and their relation to metastasis of cancer, we studied metastatic and nonmetastatic gastric carcinoma specimens by immunohistochemical staining. Among the 101 specimens examined, 37(36.6%) showed positivity in staining for p53 protein and 64(63.4%) showed no detectable p53 protein in tumor cells. p53 overexpression was correlated with depth of invasion, lymphatic invasion, lymph node metastasis and distant metastasis. Out of 101 specimens, 35 cases had no staining for nm23. 62 cases(61.4%) exhibited a cytoplasmic staining on most cells and 42 cases (41.6%) had nuclear staining. In 16 of 101 cases(15.8%), a mild to moderate membranous staining was observed in some cells. Cytoplasmic nm23 expression was negatively correlated with lymph node metastasis(P < 0.01) and distant metastasis(P < 0.01). The nuclear nm23 expression showed negative correlation with depth of invasion(P < 0.01), lymphatic invasion(P < 0.01), lymph node metastasis(P < 0.01), and distant metastasis(P < 0.04). The membranous nm23 expression revealed negative correlation with lymphatic invasion(P < 0.02), lymph node metastasis(P < 0.01) and distant metastasis(P < 0.02).
Adult ; Aged ; Aged, 80 and over ; Female ; *Gene Expression Regulation, Neoplastic ; Human ; Immunohistochemistry ; Male ; Middle Age ; Neoplasm Metastasis ; Nucleoside-Diphosphate Kinase/*analysis ; Prognosis ; Protein p53/*genetics ; Stomach Neoplasms/*chemistry/*pathology ; Support, Non-U.S. Gov't ; Transcription Factors/*genetics

The metastasis-suppressing role of the nm23 gene in the metastatic spread of malignant tumor is still debated. We examined the nm23-H1 protein expression and gene mutation in non-Hodgkin's lymphomas to compare with the clinicopathologic parameters. The expression of nm23-H1 protein was immunohistochemically examined in 150 cases of non-Hodgkin's lymphomas; 85 diffuse large B cell lymphomas (DL-BCL), 18 marginal zone B cell lymphomas (MZL), 3 mantle cell lymphomas, 25 peripheral T cell lymphomas, not otherwise specified (TCLNOS), and 19 NK/T cell lymphomas (NK/T). Eighty-one cases (58 DLBCL, 6 MZL, 4 TCLNOS, and 13 NK/T) were studied for nm23-H1 gene mutation in exon 1 to 5. The high expression of nm23-H1 protein was associated with the high IPI score (p=0.019) and the low survival rate of the patients (p=0.0039). The gene mutation of nm23-H1 was detected in 10.3% of DLBCL and 30.7% of NK/T; but none in MZL and TCLNOS. The mutation was found in exon 1 in 5 cases, exon 2 in two cases, exon 4 in one case and both exon 1 and 2 in two cases. Our results suggest that the expression of nm23-H1 protein can be used as a poor prognostic marker in non-Hodgkin's lymphomas, and the mutational change of gene may operate in the lymphomagenesis.
Tissue Array Analysis ; Survival Analysis ; Prognosis ; Polymorphism, Single-Stranded Conformational ; Nucleoside-Diphosphate Kinase/*genetics/metabolism ; Mutation/*genetics ; Middle Aged ; Male ; Lymphoma, T-Cell/genetics/metabolism/pathology ; Lymphoma, Non-Hodgkin/genetics/metabolism/*pathology ; Lymphoma, Mantle-Cell/genetics/metabolism/pathology ; Lymphoma, Large-Cell, Diffuse/genetics/metabolism/pathology ; Lymphoma, B-Cell/genetics/metabolism/pathology ; Immunohistochemistry ; Humans ; Female ; DNA Mutational Analysis ; Base Sequence