We underwent protein assay for Myc expression in 76 human gastric cancer tissues using immunohistochemistry. Expression of Myc protein was analyzed according to proliferative indices measured by flow cytometry. Levels of Myc protein expression was evaluated by correlating with biologic and clinical parameters. In 36 (47.4%) of 76 primary gastric cancers, overexpression of Myc was observed. We could observe expression of Myc protein in a significant portion of early gastric cancer (42.9%). Expression of Myc protein was demonstrated to be more frequent in poorly differentiated cancer cells (p=0.043). However, expression of Myc protein had little influence over progress or extent of the disease. Expression of Myc protein was significantly correlated with increased proliferative activity (p=0.032) and patients with high levels of Myc expression had poor disease-free survival. In a certain proportion of human gastric cancer, Myc protein may function as a regulator of cancer cell growth and expression of Myc may represent an aggressive phenotype of gastric cancer.
Adult ; Aged ; Cell Division ; Female ; Flow Cytometry ; Human ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Age ; Neoplasm Invasiveness ; Neoplasm Staging ; Proto-Oncogene Proteins c-myc/analysis* ; Stomach/pathology ; Stomach/chemistry ; Stomach Neoplasms/pathology ; Stomach Neoplasms/mortality ; Stomach Neoplasms/chemistry* ; Survival Rate

BACKGROUND/AIMS: This study reviewes the clinicopathological features, prognosis, and differences in the expression of p53 and Ki-67 immunochemical staining in squamous cell and adenosquamous carcinoma of the stomach. METHODS: From January 1995 to June 2005, 2,282 cases of gastric carcinoma were resected surgically in our hospital and 191 additional cases were resected by endoscopic mucosal resection. Retrospective pathologic review and immunochemical staining of p53 and Ki-67 were performed. RESULTS: The study consists of eight cases (0.032%) of primary squamous cell carcinoma (one case) and adenosquamous carcinoma (seven cases) without early gastric cancer. Six cases (75.0%) were male and two cases were female. The mean age was 66 year-old. The clinical presentation and physical findings did not differ from those of adenocarcinoma. The mean tumor size was 5.2+/-1.7 cm. Macroscopically, five were Borrmann type 3 (62.5%) and three were type 2. At the initial diagnosis, six (75%) were stage IV based on TNM tumor staging. Six cases (75%) progressed despite the therapy while two cases responded to the treatment. The median survival time was 11.0 months (range 4.3+/-17.7). Overexpression of p53 was seen in five cases (62.5%) and their survival was poor when compared to the p53-negative group (p=0.04). The mean Ki-67 labeling index was 70.0+/-20.8%, and was not associated with p53 staining (p>0.05). CONCLUSIONS: Adenosquamous and squamous cell carcinoma of the stomach are very rare. They tend to be at advanced stages on initial diagnosis, and progress rapidly. They show p53 protein overexpression and high Ki-67 labeling index, which might be related to poor prognosis.
Adult ; Aged ; Carcinoma, Adenosquamous/chemistry/mortality/*pathology ; Carcinoma, Squamous Cell/chemistry/mortality/*pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*analysis ; Male ; Middle Aged ; Stomach Neoplasms/chemistry/mortality/*pathology ; Survival Rate ; Tumor Suppressor Protein p53/*analysis

BACKGROUNDFOXP3 was thought to express in the T-cell lineage exclusively until recently when FOXP3 was shown to be expressed by cancer cells. It was indicated that FOXP3 may play a wider role in biology by endowing tumor cells with immune suppressive activity. However, researches between FOXP3 and lymph node metastasis of gastric cancer were relatively infrequent, so the present work was aimed to investigate the relationship between FOXP3 expression and lymph node metastasis in human gastric cancer.

METHODSA total of 122 gastric cancer patients were enrolled in this study, and gastric tumor specimens and lymph nodes were acquired. Thirty patients who had chronic superficial gastritis diagnosed by gastroscopy contemporaneously in the Peking University People's Hospital were chosen randomly as the control group. Immunohistochemistry was performed to evaluate FOXP3 expression. A survival analysis on the 122 patients was then performed. Then, NCI-N87 cell lines were used to confirm FOXP3 expression in gastric carcinoma cells. Finally, evaluation of FOXP3 expression in gastric tumor and peritumor tissues in 12 patients were conducted using immunohistochemistry and Western blotting. A χ(2) test or Fisher's exact test (bilateral) was conducted to compare the percentage of positive percentage staining between groups. Kaplan-Meier analysis was performed for survival analysis.

RESULTSFOXP3 was expressed by gastric cancer cells and peritumor epithelial cells. FOXP3 expression was increased in primary tumors (58.2%) than that in control group (26.7%). In the lymph-node metastasis group, the incidence of lymph node metastasis which was less than 60% had a significant upregulation of FOXP3 in primary tumors and lymph nodes. However, the frequency of FOXP3 expression had no relationship with survival.

CONCLUSIONFOXP3 probably has a relationship with lymph node metastasis of gastric cancer.

Adult ; Aged ; Blotting, Western ; Cell Line, Tumor ; Epithelial Cells ; chemistry ; Female ; Forkhead Transcription Factors ; analysis ; physiology ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Stomach Neoplasms ; chemistry ; mortality ; pathology

BACKGROUNDInsulin-like growth factor-II mRNA-binding protein 3 (IMP3) is a newly identified mRNA-binding protein that is involved in embryogenesis and carcinogenesis of some malignant tumors. The aim of this study was to detect the expression of IMP3 protein in gastric adenocarcinoma (GAC) and the correlation with clinicopathological features.

METHODSIMP3 protein in 92 samples of GAC was evaluated by immunohistochemical method. The Mann-Whitney U test and Kruskal-Wallis H test were used to compare IMP3 expression and clinicopathological parameters. Kaplan-Meier survival curve, log-rank test and Cox-regression model were used to evaluate the correlation of IMP3 protein expression to the prognosis of patients.

RESULTSOut of 92 cases of adjacent normal mucosa (ANM), 10 with dysplasia demonstrated weak expression of IMP3 and 82 without dysplasia showed negative expression. Out of 92 cases of GAC, positive immunohistochemical stain for IMP3 was identified in 75 (82%) cases. A comparison of IMP3 expression in GAC and ANM showed stronger immunohistochemical reactivity in GAC (P < 0.05). High expression of IMP3 was found to be associated with lymphoid metastasis, high Ki-67 labelling index, and patient poor outcome (P < 0.05). There was a significant TNM stage difference between GAC with and without IMP3 expression (P < 0.05). Tumors with higher stage showed higher level of IMP3 expression. In multivariate analysis, IMP3 emerged as an independent predictor of survival.

CONCLUSIONSIncrease of IMP3 expression suggests that IMP3 may play an importent role in the carcinogenesis and tumor metastasis in GAC. It could be regarded as a novel proliferation and prognostic indicator for patients with GAC.

Adenocarcinoma ; chemistry ; mortality ; pathology ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; analysis ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; analysis ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA-Binding Proteins ; analysis ; physiology ; Retrospective Studies ; Stomach Neoplasms ; chemistry ; mortality ; pathology

152 curative gastrectomy specimens from patients with gastric carcinoma were examined in an attempt to assess the prognostic value of c-erbB-2 and mutant p53 protein expressions. The labeled streptavidin-biotin method was applied to routinely fixed and paraffin-embedded tissue sections, using the polyclonal and monoclonal antibodies against the c-erbB-2 protein and the mutant form p53 protein, respectively. In this examination, staining of c-erbB-2 protein was found in 9.2% of these carcinomas. The c-erbB-2 stained tumors were significantly associated with the tumors whose diameters were smaller than 5cm, and were more likely to be associated with serosal invasion and nodal involvement than the unstained ones. However, there was little association between staining of c-erbB-2 protein and clinicopathologic findings such as age, sex, location, histology, gross type, lymph node status, depth of invasion, and stage. The survival analysis of 104 patients with stage III gastric carcinoma revealed no significant association between c-erbB-2 staining status and survival duration. The 5-year survival rates of the c-erbB-2 positive group and its negative group were 21% and 28%, respectively. Positive p53 protein expression was observed in 46% of 152 carcinomas. There was no significant association between p53 expression and parameters such as age, sex, location, histology, gross type, and size. The p53 stained tumors were more likely to be associated with lymph node metastasis, serosal invasion than p53 unstained ones; but this did not reach significance. The 5-year survival rates of the p53 positive group and counter part group were 27% and 31%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult ; Aged ; Female ; Human ; Male ; Middle Age ; Multivariate Analysis ; Prognosis ; Protein p53/*analysis ; Receptor, erbB-2/*analysis ; Stomach Neoplasms/*chemistry/mortality ; Survival Rate

It has been reported that p53 mutation may contribute to upregulate cyclooxygenase (COX)-2 expression that is observed in malignant tissues. These molecules are involved in carcinogenesis by affecting tumor cell proliferation. The aim of this study was to examine the relationship between COX-2 or p53 expression and clinico-pathological characteristics including tumor cell proliferation in gastric cancer. COX-2 and p53 expressions were investigated with immunostaining, in tissue specimens obtained from 119 patients who underwent surgery for gastric cancer. The Ki-67 labeling index (LI) was counted by Ki-67 immunostaining. COX-2 and p53 expressions correlated significantly with depth of tumor invasion. However, there was no association between COX-2 or p53 expression and survival. p53 expression did not correlate with COX-2 expression. There was no significant difference in various clinicopathological variables between Ki-67 LI subgroups. The mean Ki-67 LI value of COX-2 positive tumors was significantly higher than that of negative tumors. The mean Ki-67 LI value of p53 positive tumors was not significantly higher than that of negative tumors. The mean Ki-67 LI value of both COX-2 and p53 positive tumors was significantly higher than that of both negative tumors. These results imply that COX-2 expression is associated with tumor cell proliferation of gastric cancer.
Tumor Suppressor Protein p53/*analysis ; Stomach Neoplasms/*chemistry/mortality/pathology ; Prognosis ; Middle Aged ; Male ; Ki-67 Antigen/*analysis ; Immunohistochemistry ; Humans ; Female ; Cyclooxygenase 2/*analysis ; Aged ; Adult

To elucidate the clinical significance of phenotypic alterations of Lewis antigen in gastric cancer patients, we investigated Lewis antigens by analyzing the genotypes of the Le and Se genes and by comparing the results obtained with the phenotypic expression of Lewis antigen in gastric cancer tissue and blood cells. One hundred and twenty gastric cancer patients were examined and compared with respect to Lewis blood phenotype and genotype. The expression of Lea, Leb, sialylated Lea, and sialylated Lex antigens was immunohistochemically examined in uninvolved gastric mucosa, intestinal metaplasia, and cancerous tissue. We also analyzed the significance of Lewis antigen expression by analyzing patient survival. The frequencies of the Lewis phenotypes of RBCs corresponding to Le(a+b-), Le(a-b+), and Le(a-b-) were 16%, 58%, and 26%, respectively. The Le and le allele gene frequencies calculated from genotyping in gastric cancer patients were 0.623 and 0.377, respectively. The frequency for Le(a-b-) of the RBC phenotype had a tendency to be higher in cancer patients than in normal healthy Koreans. However, no difference in the Lewis gene frequency was found between these gastric cancer patients and healthy persons. The phenotype of Le(a-b+) was most prevalent in uninvolved gastric mucosal tissue, whereas the most prevalent form in tumor tissue was Le(a-b-). Sialyl-Lea and sialyl-Lex antigens were hardly detectable in uninvolved gastric mucosa, whereas the two antigens were expressed highly in intestinal metaplastic mucosa and tumor cells. In conclusion, the loss of Lewis antigen expression in tissue and on RBCs in gastric cancer patients is not a result of genetic influences, but rather a result of sialylation in tissue. We also confirm that poor prognosis is associated with dimeric sialyl-Lex and vascular spread.
Adult ; Aged ; Alleles ; Erythrocytes/*chemistry ; Female ; Fucosyltransferases/*analysis/genetics ; Gangliosides/analysis ; Genotype ; Human ; Immunohistochemistry ; Male ; Metaplasia ; Middle Age ; Oligosaccharides/analysis ; Phenotype ; Stomach Neoplasms/*blood/genetics/mortality

OBJECTIVEParaaortic lymph nodes dissection in advanced gastric carcinoma is controversial. Investigation of micrometastasis in these critical lymph nodes is important in the evaluation of prophylactic lymphadenectomy.

METHODSA total of 2 339 lymph nodes, including 390 paraaortic nodes, obtained from 47 patients with advanced gastric carcinoma were examined immunohistochemically using cytokeratin antibody.

RESULTSParaaortic lymph node metastasis was found in 95 of 390 nodes of 14 patients by routine histological examination. Micrometastasis in the paraaortic lymph nodes was immunohistochemically detected in 45 of 295 negative nodes from 15 of 33 patients. The 5-year-survival rate in patients with paraaortic lymph node metastasis was 56.0% in the node negative group, 25.2% in the cytokeratin positive group and 9.0% in the hematoxilin and eosin positive group.

CONCLUSIONSWe have demonstrated a high rate of micrometastasis in the paraaortic lymph nodes of patients with advanced gastric carcinoma and have confirmed that prophylactic lymphadenectomy of these nodes is effective for such patients.

Adult ; Aged ; Female ; Humans ; Immunohistochemistry ; Keratins ; analysis ; Lymph Nodes ; chemistry ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Stomach Neoplasms ; mortality ; pathology ; Survival Rate

OBJECTIVE: To investigate the differentially expressed genes between gastric cancer and normal gastric mucosa by bioinformatics analysis, identify the important gene participating in the occurrence and progression of gastric cancer, and predict the functions of these genes. METHODS: The gene expression microarray data GSE100935 (including 18 gastric cancer samples and normal gastric mucosal tissues) downloaded from the GEO expression profile database were analyzed using Morpheus to obtain the differentially expressed genes in gastric cancer, and a cluster analysis heat map was constructed. The online database UALCAN was used to obtain the expression levels of these differentially expressed genes in gastric cancer and normal gastric mucosa. The prognostic value of the differentially expressed genes in gastric cancer was evaluated with Kaplan-Meier survival analysis. GO functional enrichment analysis was performed using Fun-Rich software, and the STRING database was exploited to establish a PPI network for the differentially expressed genes. RESULTS: A total of 45119 differentially expressed genes were identified from GSE100935 microarray data. Analysis with UALCAN showed an obvious high expression of EXD3 gene in gastric cancer, and survival analysis suggested that a high expression level of EXD3 was associated with a poorer prognosis of the patients with gastric cancer. GO functional enrichment analysis found that the differentially expressed genes in gastric cancer were involved mainly in the regulation of nucleotide metabolism and the activity of transcription factors in the cancer cells. CONCLUSIONS EXD3 may be a potential oncogene in gastric cancer possibly in relation to DNA damage repair. The up-regulation of EXD3 plays an important role in the development and prognosis of gastric cancer, and may serve as an important indicator for prognostic evaluation of the patients.
Computational Biology ; Databases, Genetic ; Exonucleases ; genetics ; Gastric Mucosa ; chemistry ; enzymology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins ; genetics ; Prognosis ; Stomach Neoplasms ; enzymology ; genetics ; mortality

There is increasing evidence that genes involved in normal cell growth and differentiation (oncogenes) or genes that encode for growth factors are important in determining the development and biologic aggressiveness of gastric carcinoma. This study was undertaken to define the prognostic value of the overexpression of p53 protein, c-erbB-2 protein, EGFr protein and PCNA in gastric carcinomas. Using monoclonal antibodies, immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections from 84 primary gastric carcinomas. Overall, 34% of gastric carcinomas had nuclear-staining for p53 protein, 34% of carcinomas membrane staining for the c-erbB-2 and 74% of carcinomas membrane and cytoplasmic staining for EGFr, showing distribution in a heterogeneous fashion. PCNA was expressed as Grade 2 and 3 in 75% of patients with gastric carcinomas. Both c-erbB-2 and p53 staining was significantly associated with high grade expression of PCNA. p53 staining tended to be associated with positive nodal status and metastasis, and c-erbB-2 staining with positive nodal status only. Multivariate analysis using the Cox model showed that overexpression of p53 protein, c-erbB-2 protein and PCNA was not an independent prognostic variable in gastric carcinoma. These results suggest that expressions of p53 and c-erbB-2 protein are heterogeneous and that p53 and c-erbB-2 overexpressions are significantly associated with high proliferative activity in gastric carcinoma.
Antigens, Neoplasm/analysis ; Humans ; Immunohistochemistry ; Multivariate Analysis ; Neoplasm Proteins/analysis ; Nuclear Proteins/*analysis ; Prognosis ; Proliferating Cell Nuclear Antigen ; Proto-Oncogene Proteins/*analysis ; Receptor, Epidermal Growth Factor/*analysis ; Receptor, erbB-2 ; Retrospective Studies ; Stomach Neoplasms/*chemistry/immunology/mortality ; Survival Rate ; Tumor Suppressor Protein p53/*analysis