Abnormal expression of E-cadherin/catenin complex in cancer has been associated with poor differentiation and acquisition of invasiveness, suggesting a possible role of this protein as an invasion suppressor. In this study, we conducted an immunohistochemical investigation of all components of the E-cadherin/catenin complex in 65 gastric cancer patients. Abnormal expression of E-cadherin and, alpha- and gamma-catenin occurred more frequently in diffuse than in intestinal type of gastric cancer, and correlated with poor differentiation. Abnormal expression of E-cadherin and beta-catenin correlated with poor survival. Abnormal expression of all four components of the complex was associated with poorly differentiated and diffuse-type carcinoma, and poor survival. In the multivariate analysis, abnormal expression of the E-cadherin/catenin complex was not an independent prognostic factor. These results suggest that the E-cadherin/catenin complex may be a useful marker of differentiation and prognosis in gastric cancer. Further studies are warranted to clarify the impact of the E-cadherin/catenin complex on prognostic factor of gastric cancer.
Adult ; Aged ; Cadherins/biosynthesis* ; Cytoskeletal Proteins/biosynthesis* ; Female ; Human ; Male ; Middle Age ; Prognosis ; Stomach Neoplasms/pathology ; Stomach Neoplasms/metabolism* ; Survival Analysis ; Tumor Markers, Biological/biosynthesis*

To study the expression of hypoxia inducible factor-1alpha (HIF-1alpha) protein in prostate cancer (Pca) and its biological significance, the expression of HIF-1alpha was assayed by means of immunohistochemical technique in 42 prostate cancer, 12 prostatic intraepithelial neoplasm (PIN) and 9 normal prostate tissue (NP) specimens. Western blot was used to examine the expression of HIF-1alpha in prostate cancer cell line (PC-3M) induced by different oxygen tension. HIF-1alpha expression was positive in 33 Pca and 9 PIN specimens, and the positive rate of HIF-1alpha was higher in distant metastasis patients than in patients without metastasis of prostate cancer (P<0.05), while there was no expression of HIF-1alpha in NP. The level of HIF-1alpha in PC-3M significantly increased with the decrease of oxygen tension (P<0.01). Overexpression of HIF-1alpha is the preliminary event of the formation of Pca, which may induce carcinoma into malignant phenotype. Thus it may serve as an early diagnosis marker and the novel target for Pca treatment.
Adenocarcinoma/*metabolism ; Cell Line, Tumor ; Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Prostatic Neoplasms/*metabolism ; Tumor Markers, Biological/*biosynthesis

In order to investigate the expression levels of Pin1 mRNA and protein in cervical cancer and its association with Ki67 and their clinical significance, amplification of Pin1 gene was examined by RT-PCR, and the expression of both Pin1 and Ki67 protein was detected by immunohistochemistry in cervical cancer tissues. It was shown that the expression levels of Pin1 were higher in cervical cancer than in normal cervical tissues (P < 0.05). The expression of Pin1 protein was increased progressively along with the disease process from normal cervix to CIN and to cervical cancer (P < 0.05). No significant difference in the Pin1 expression was found between disease stages (FIGO), pathological grades or pelvic lymph node metastasis status (P > 0.05). The expression of Pin1 was significantly higher in adenocarcinoma than in squamous carcinoma of the uterine cervix (P < 0.05). In cervical cancer, the overexpression of Pin1 was positively correlated with that of Ki67 (P < 0.05). These results suggested that the overexpression of Pin1 was closely related with cancer cell proliferation or progression of cervical cancer and contributed to oncogenesis. Pin1 may serve as a potential marker for cervical cancer diagnosis.
Cervical Intraepithelial Neoplasia/metabolism ; Ki-67 Antigen/*biosynthesis ; Ki-67 Antigen/genetics ; Peptidylprolyl Isomerase/*biosynthesis ; Peptidylprolyl Isomerase/genetics ; Tumor Markers, Biological ; Uterine Cervical Neoplasms/*metabolism

In order to study the expressions of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in human laryngeal squamous cell carcinoma (LSCC) and its significance, the expression of VEGF mRNA and COX-2 mRNA in 62 cases of LSCC and 54 adjacent noncancerous laryngeal tissues and 9 normal human laryngeal mucous tissues was detected by using techniques of semi-quantitative RT-PCR. It was found that the expression level of VEGF and COX-2 mRNA was significantly increased in LSCC as compared with that in the normal human laryngeal mucous tissues (both P < 0.01), and the expression level of VEGF and COX-2 mRNA were significantly increased in stage Ill + IV tissues of LSCC as compared with the stage I + II tissues of LSCC (P < 0.01). There was a high positive correlation between VEGF and COX-2 expression in LSCC (r = 0.756, P < 0.01). These data raise the possibility that VEGF and COX-2 may play key roles in the growth, invasion and metastasis of LSCC.
Carcinoma, Squamous Cell/*metabolism ; Cyclooxygenase 2/*biosynthesis ; Cyclooxygenase 2/genetics ; Laryngeal Neoplasms/*metabolism ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Tumor Markers, Biological ; Vascular Endothelial Growth Factor A/*biosynthesis ; Vascular Endothelial Growth Factor A/genetics

Although N-myc downstream regulated gene 2 (NDRG2) has been known to be a tumor suppressor gene, the function of this gene has not been elucidated. In the present study, we investigated the expression and function of NDRG2 in human gastric cancer. Among seven gastric cancer and two non-cancer cell lines, only two gastric cancer cell lines, SNU-16 and SNU-620, expressed NDRG2, which was detected in the cytoplasm. Interestingly, NDRG2 was highly expressed in normal gastric tissues, but gastric cancer patients were divided into NDRG2-positive and -negative groups. The survival rate of NDRG2-negative patients was lower than that of NDRG2-positive patients. We confirmed that the loss of NDRG2 expression was a significant and independent prognostic indicator in gastric carcinomas by multivariate analysis. To investigate the role of NDRG2 in gastric cancer cells, we generated a NDRG2-silenced gastric cancer cell line, which stably expresses NDRG2 siRNA. NDRG2-silenced SNU-620 cells exhibited slightly increased proliferation and cisplatin resistance. In addition, inhibition of NDRG2 decreased Fas expression and Fas-mediated cell death. Taken together, these data suggest that inactivation of NDRG2 may elicit resistance against anticancer drug and Fas-mediated cell death. Furthermore, case studies of gastric cancer patients indicate that NDRG2 expression may be involved in tumor progression and overall survival of the patients.
Apoptosis/*physiology ; Cell Line, Tumor ; Down-Regulation ; Fas Ligand Protein/*physiology ; Gene Expression Regulation, Neoplastic ; Humans ; Stomach Neoplasms/metabolism/*mortality/pathology ; Tumor Markers, Biological/*metabolism ; Tumor Suppressor Proteins/biosynthesis/genetics/immunology/*metabolism

Recently diffuse large B cell lymphoma (DLBCLs) was reported to be subdivided into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subgroups by using cDNA microarray and immunohistochemical markers. Tissue microarray blocks were created from 51 nodal DLBCLs with control tissue. Immunohistochemical staining for the above markers were performed. The median follow-up period was 26 months. Nodal DLBCLs were subclassified into GCB [CD10+ or CD10-/Bcl-6+/MUM1-, n=17 (33%)] and non-GC subgroups [CD10-/Bcl-6- or CD10-/Bcl-6+/MUM1+, n=35 (67%)], and were alternatively subclassified into pattern A [+ for GCB marker only, n=12 (23%)], B [Co-positive for both markers, n=13 (33%)], C [+ for activation marker only, n=18 (35%)], and D [- for both markers, n=9 (17%)]. Upon survival analysis, the GCB groups showed a relatively better survival than non-GC groups (p=0.0748). Also, pattern C (p=0.0055) and CD138+ (p=0.0008) patients had significantly lower survival rates. By multivariate analysis, CD138 expression alone was considered as an independent risk factor (p=0.031). In summary, our results add to the registration of prognostic implications for previously reported DLBCL subgroups. CD138 may play an important role as a poor prognostic marker. By using immunohistochemistry, a prognostically important subclassification of DLBCLs is possible.
Tumor Markers, Biological/metabolism ; Syndecans/metabolism ; Syndecan-1/*biosynthesis ; Prognosis ; Neprilysin/biosynthesis ; Middle Aged ; Male ; Lymphoma, Large-Cell, Diffuse/*diagnosis/*metabolism/pathology ; Lymphoma, B-Cell/*diagnosis/*metabolism/pathology ; Humans ; *Gene Expression Regulation, Neoplastic ; Female ; Aged, 80 and over ; Aged ; Adult

Gastric cancer is a very serious disease and is naturally resistant to many anticancer drugs. To reduce the mortality and improve the effectiveness of therapy, many studies have tried to find key biomarkers. Proteomic technologies are providing the tools needed to discover and identify disease-associating biomarkers. The proteomic study of gastric cancer establishes any specific events that lead to cancer, and it provides a direct way to define the true function of genes. Using two dimensional (2-D) electrophoresis of the stomach cancer tissue, we have gained about 1,500 spots in each gel, and 140 protein spots also were identified. Among the identified proteins, there were seven over-expressed proteins in stomach cancer tissue: NSP3, transgelin, prohibitin, heat shock protein (hsp) 27 and variant, protein disulfide isomerase A3, unnamed protein product and glucose regulated protein. There were also seven under-expressed proteins in stomach cancer: Apolipoprotein A-1, p20, nucleoside diphosphate isomerase A, alpha 1 antitrypsin, desmin, serum albumin and sero-transferrin.
Aged ; Carrier Proteins/biosynthesis ; Cell Line, Tumor ; Electrophoresis, Gel, Two-Dimensional ; Female ; Human ; Male ; Microfilament Proteins/biosynthesis ; Middle Aged ; Muscle Proteins/biosynthesis ; Neoplasm Proteins/biosynthesis ; Proteins/biosynthesis ; *Proteome ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Stomach Neoplasms/*metabolism ; *Tumor Markers, Biological

This study was aimed to evaluate the prevalence and prognostic implication of thyroid transcription factor-1 (TTF-1) immunoreactivity in 81 human lung carcinomas, including 65 cases of non-small cell lung carcinoma (NSCLC) and 16 cases of small cell lung carcinoma (SCLC); and also to investigate its relationship with the cell proliferation and regulation by immunostaining of Ki-67 and p53 proteins, respectively. The immunohistochemical staining for TTF-1(clone 8G7G3/1) was performed and several clinicopathologic variables and the follow-up data were obtained. The immuno-staining results for TTF-1 were semiquantitatively interpreted as negative and positive. Of NSCLCs, TTF-1 is highly expressed in adenocarcinomas (76%), whereas squamous cell carcinomas revealed no immunoreactivity (0%). SCLCs showed strong TTF-1 expression (88%). In NSCLC, TTF-1 expression was inversely correlated with Ki-67 proliferative activity and independent of p53 overexpression. TTF-1(+) group tended to show better survival than TTF-1(-) group in NSCLC. Conclusively, these observations suggest that TTF-1 is a sensitive and specific diagnostic marker for pulmonary adenocarcinomas and SCLCs; that TTF-1 might have a good prognostic implication based on its inverse correlation with Ki-67 proliferative activity and tendency for better survival in NSCLC; that this cell lineage marker may play a role in the molecular pathogenesis of lung cancers at the level of transcription.
Adenocarcinoma/diagnosis/metabolism ; Adult ; Aged ; Carcinoma, Non-Small-Cell Lung/diagnosis/*metabolism/mortality ; Carcinoma, Small Cell/diagnosis/*metabolism/mortality ; Cell Division ; Cell Line, Tumor ; Cell Lineage ; Female ; Human ; Immunohistochemistry ; Ki-67 Antigen/*biosynthesis ; Lung Neoplasms/diagnosis/*metabolism/mortality ; Male ; Middle Aged ; Nuclear Proteins/*biosynthesis ; Prognosis ; Protein p53/*biosynthesis ; Sensitivity and Specificity ; Time Factors ; Transcription Factors/*biosynthesis ; Transcription, Genetic ; Tumor Markers, Biological

Gastric cancer is one of the most common cancers worldwide. The purpose of this study was to find out potential markers for gastric cancer. Tumor and normal tissues from 152 gastric cancer cases were analyzed by two-dimensional gel electrophoresis (2-DE). The images of silver stained gels were analyzed and statistical analysis of spot intensities revealed that spot 4262 showed higher expression (5.7-fold increase) in cancer tissues than in normal tissues (P< 0.001). It was identified by peptide mass fingerprinting as nicotinamide N-methyltransferase (NNMT). A monoclonal antibody with a detection limit down to 10 ng was produced against NNMT in mouse. Using the prepared monoclonal antibody, western blot analysis of NNMT was performed for gastric tissues from 15 gastric cancer patients and two gastric ulcer patients. The results corroborated those of 2-DE experiments. A single spot was detected in gastric ulcer tissues while four to five spots were detected in gastric cancer tissues. In cancer tissues, two additional spots of acidic and basic form were mainly detected on 2-DE gels. This suggests that NNMT receives a post-translational modification in cancer- specific manner.
Tumor Markers, Biological/isolation & purification ; Tissue Distribution ; Stomach Ulcer/metabolism ; Stomach Neoplasms/*metabolism ; Proteome/analysis ; *Protein Processing, Post-Translational ; Phosphorylation ; Nicotinamide N-Methyltransferase/immunology/*metabolism ; Mice, Inbred BALB C ; Mice ; Humans ; Carcinoma/*metabolism ; Blotting, Western/methods ; Antibodies, Monoclonal/biosynthesis ; Animals

The Wnt signaling pathway has regulatory roles in cell proliferation, differentiation, and polarity. Aberrant Wnt pathway regulation can lead to abnormal cell proliferation and cancer, and loss of Wnt7a expression has been demonstrated in lung cancer cell lines. E-cadherin keeps intercellular integrity and prevents metastasis. Therefore, E-cadherin has been known as a prognostic factor in cancer. In the present study, we investigated the E-cadherin expression status by immunohistochemical stain and the Wnt7a promoter methylation status in human non-small cell lung carcinoma (NSCLC) by methylation-specific PCR. We also analyzed their correlations with clinicopathological factors. Methylation of the Wnt7a gene promoter was detected in the lung tissues of 32 of 121 (26.4%) patients with NSCLC. Wnt7a promoter methylation was correlated with advanced tumor stage (P = 0.036) and distant metastasis (P = 0.037). In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001). However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit. Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.
Cadherins/biosynthesis ; Carcinoma, Non-Small-Cell Lung/*genetics/mortality ; DNA Methylation/*genetics ; Female ; Humans ; Lung Neoplasms/*genetics/mortality ; Male ; Middle Aged ; Neoplasm Metastasis/genetics ; Neoplasm Staging ; Promoter Regions, Genetic/*genetics ; Republic of Korea ; Tumor Markers, Biological/genetics ; Wnt Proteins/*genetics