Detection of Frameshift Mutations of the Transforming Growth Factor β Receptor Ⅱ in Gastric Cancers with Microsatellite Instability

OBJECTIVE To study the relationship among microsatellite instability （MSI）, frameshift mutations （FM） of the transforming growth factor β receptor Ⅱ （TGF β R Ⅱ）, methylation state of the hMLH1 promoter and hMLH1 protein expression level in gastric cancers, and to explore their relationship to gastric carcinogenesis. METHODS DNA was isolated from 101 gastric specimens and 5 microsatellite loci were detected. PCR, electrophoresis on denatured polyacrylamide gels and silver staining were performed to detect the MSI. The FMs of TGFβR Ⅱ were also screened with the same method. HMLH1 methylation was analyzed by methylation specific PCR （MSP） and sequencing. HMLH1 protein expression was detected using immunohistochemistry. RESULTS The incidence of MSIs was 53.7% and 0% in the cancers and normal tissues, respectively, with the frequency of MSIs being significantly higher in the gastric cancers compared to the normal gastric tissues （P〈0.05）. The frequency of hMLH1 methylation was 41.5%（17/41） in the gastric cancers and 0%（0/60） in the normal group. Decreased hMLH1 expression was observed in 94.1%（16/17） of cases exhibiting methylation. FMs of TGFβR Ⅱ were identified in 5 （62.5%） of the 8 samples with MSIH. In contrast, FMs were not found in MSI-L or microsatellite stable （MSS） cases. CONCLUSION MSIs and FMs of TGFβR Ⅱ may play an important role in gastric carcinogenesis. HMLH1 methylation is an important modification of the DNA which results in inactivation of hMLH1 and mismatch repair defects which lead to MSls and FMs of TGFβR Ⅱ.     

Analysis of Inactivation of hMLH1 by Promoter Hypermethylation and Microsatellite Instability in Gastric Carcinogenesis

OBJECTIVE To study the microsatellite instability (MSI) and methylation state of the hMLH1 gene promoter and their mechanisms underlying the development of gastric cancer. METHODS Forty-one gastric cancer samples were obtained from patients undergoing surgery and 46 chronic atrophic gastritis tissues with dysplasia or intestinal metaplasia (IM) were obtained from patients undergoing gastro-endoscopy. Fourteen normal gastric mucosal samples were used as controls. Genomic DNA was extracted from the samples and 5 microsatellite markers were used to measure MSI. Methylation-specific PCR (MSP) was used to screen the methylation state of the samples. DNA sequencing and immunohistochemistry were performed to verify the results. RESULTS MSI was identified in 22 out of the 41 (53.7%) gastric cancers, of which 8 cases showed high-level MSI (2 or more loci altered) and 14 showed low-level MSI (1 locus altered). MSI was also detected in 12 out of 46 (26.1%) pre-cancerous lesions of the stomach, whereas it was not seen in the normal tissue. Moreover, hMLH1 hypermethylation was detected in 17 out of the 41 (41.5%) gastric cancers, 9 out of the 46 (19.6%) pre-cancerous lesions and 0 out of the 14 normal tissue. Significant differences in frequency of MSI and hMLH1 promoter methylation were observed among gastric cancers, precancerous lesions and normal gastric tissue. Gastric samples with MSI had a tendency to be hypermethylated in the hMLH1 promoter. DNA sequencing and immunohistochemistry results also confirmed that hMLH1 promoter methylation could lead to loss of the hMLH1 protein and gene silence which sequentely resulted in gene mismatch and MSI. CONCLUSION Accumulation of MSI and hMLH1 promoter methylation may be important early molecular events during gastric carcinogenesis and may contribute to the acquisition of a transformed cell phenotype and the development of gastric cancer.     

The Role of Expression of Mismatch Repair Proteins hMSH2 and hMLH1 in Gastric Carcinogenesis and its Clinical Significance

OBJECTIVE To investigate the expression of the mismatch repair proteins hMSH2 and hMLH1,and to examine the clinical significance of the intracellular expression site(ICES)in gastric carcinogenesis. METHODS Specimens from 172 cases of gastric cancer,151 tissues from paraneoplastic gastric mucosa and 34 from noncancerous gastric mucosa were collected in Dalain,China.An immunohistochemical method was used to determine the expression of the hMSH2,hMLH1 proteins and their ICES in the gastric mucosas. RESULTS The rate of hMSH2 expression in gastric cancers,paraneoplastic gastric mucosas and noncancerous gastric mucosas were respectively 69.8%,49.7%and 32.4%.The rate was significantly higher in gastric cancer compared to the latter two groups(P=0.000),but there was no obvious difference in the expression between the two latter groups(P=0.067). The hMLH1 protein expression rates were respectively 73.3%,57.6%and 41.2%in the above three groups.The expression was significantly higher in the gastric cancer group compared to the two latter groups(P=0.000),while there was no significant difference between the latter groups(P=0.082). There was no obvious correlation between the hMSH2 and hMLH1 protein expression rates and related factors,such as gender,age and differentiated level of gastric cancer etc.The cell-nuclear expression of the hMSH2 protein was respectively 70.0%,58.7%and 36.4%in the gastric cancer,paraneoplastic gastric mucosa and noncancerous gastric mucosa groups.The cytoplasmic expression rates were 30.0%,41.3%and 63.6%in the three groups. The cell-nuclear expression rate of the hMSH2 protein gradually decreased in the gastric mucosas in the fol owing order:cancer,paraneoplastic and noncancerous but cytoplasmic expression only increased slightly in these groups(r=0.161,P=0.020).There was no significant difference in the ICES of the hMLH1 protein among the three different gastric mucosas(P=0.659). CONCLUSION Simultaneous determination of the expression and ICES of the mismatch repair proteins hMSH2 and hMLH1 in the gastric mucosa may be helpful in detecting early gastric cancer.     

Biological Significance and the Related Molecular Mechanism of Ets1 mRNA Expression in Lung Cancer by Tissue Microarray(TMA)

Objective: To investigate the expressions and molecular mechanism of Ets-1 mRNA, and TGFβ1 and c-Met proteins in the pathogenesis, progression of lung cancer by tissue microarray (TMA) method. Methods: The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were detected in 89 primary lung cancers, 12 lung cancer with lymph-node metastasis and 12 precancerous lesions by FISH(fluorescence in situ hybridization) and immunohistochemical method, and 10 normal lung tissues were used as controls. Results: The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were significantly higher in 89 primary lung cancer than in the control group (P<0.05). The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were related to lymph node metastasis and clinical stages. There was a positive correlation between the Ets-1 mRNA expression and TGFβ1 and c-Met proteins (P<0.05). Conclusion: Ets-1 mRNA, TGFβ1 and c-Met proteins may be related to the pathogenesis, progression and malignant behavior of lung cancer. They may play an important role in prognosis assessment of lung cancer.     

Aberrant Expression of Notch1 in Cervical Cancer

OBJECTIVE To investigate the putative role of the Notch1 receptor in cervical cancer carcinogenesis and progression. METHODS The expression of the Notch1 protein was analyzed by a Western-blotting approach in 40 cervical cancer and 30 normal cervical tissues. Some tissues were examined using RT-PCR to determine mRNA levels. Celluar localization of the Notch1 protein in the paraffin-embedded cervical tissues was also analyzed by immunohistochemistry. RESULTS The Notch1 protein was detected in all 30 normal cervical tissues. In contrast, only 6 samples of 40 cervical cancer tissues showed Notch1 expression. The level of the Notch1 protein expression was significantly lower in cervical cancer tissues than that in normal tissue samples. In agreement with these observations, levels of Notch1 mRNA were found to be substantially down-regulated in cervical cancer tissues. In the immunohistochemistry staining assay, the Notch1 protein was shown to localize predominantly in the cytoplasm and nucleoli of the normal cervical squamous epithelium of the cervix, but no staining was observed in the cervical cancer cells. Notch1 expression was observed to correlate with the clinical disease stage, but there were no correlations with age, tumor size, grade or lymph node metastasis （P〉0.05）. The levels of Notch1 protein expression were significantly higher in early stages （Ⅰ-Ⅱa, 66.7%） compared to those in the advanced stages （Ⅱb～Ⅳ,12.6%）（P=0.001）. CONCLUSION Notch1 may play a role as a tumor suppressor in cervical tumorigenesis. Determination of Notch1 expression may be helpful for preoperative diagnosis and accuracy of staging. But its clinical use for cervical cancer requires further investigation.     

Gene Expression Profile Differences in Gastric Cancer and Normal Gastric Mucosa by Oligonucleotide Microarrays

OBJECTIVE To study the difference of gene expression in gastric cancer (T) and normal tissue of gastric mucosa (C), and to screen for associated novel genes in gastric cancers by oligonucleotide microarrays. METHODS U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T and C. Bioinformatics was used to analyze the detected results. RESULTS When gastric cancers were compared with normal gastric mucosa, a total of 270 genes were found with a difference of more than 9 times in expression levels. Of the 270 genes, 157 were up-regulated (Signal Log Ratio [SLR] ≥3), and 113 were down-regulated (SLR ≤-3). Using a classification of function, the highest number of gene expression differences related to enzymes and their regulatory genes (67, 24.8%), followed by signal-transduction genes (43,15.9%). The third were nucleic acid binding genes (17, 6.3%), fourth were transporter genes (15, 5.5%) and fifth were protein binding genes (12, 4.4%). In addition there were 50 genes of unknown function, accounting for 18.5%. The five above mentioned groups made up 56.9% of the total gene number. CONCLUSION The 5 gene groups (enzymes and their regulatory proteins, signal transduction proteins, nucleic acid binding proteins, transporter and protein binding) were abnormally expressed and are important genes for further study in gastric cancers.     

用基因芯片筛选胃黏膜癌变相关基因

Objective： To study the difference of gene expression and screen the carcinogenesis associated gene in gastric mucosa by oligonucleotide microarray. Methods： Using the U133A gene chip to detect the gene expression profile difference between pericancerous mucosa （mucosa inside nearly 2 cm by cancer） and normal section of gastric mucosa. Bioinformatics was used to analyze the detected result on their localization and function in chromosome. Results＂ （1） A total of 150 genes with a difference of more than 3 times in expression levels by comparing the pericancerous mucosa with normal gastric mucosa, of 130 genes were up-regulated （SLR〉I.5）, and 20 were down- regulated （SLR〈 -1.5）. From the gene expression difference was to do the function classification, among those 22 enzyme and 6 enzyme regular genes were most one （18.7%）. The next were 17 nucleic acid binding associated genes （11.3%）. The third were 15 signal transduction associated genes （10%）. Fourth, were 13 protein binding associated genes （8.7%）. Besides the 40 genes were unknown their function, above mentioned 4 groups were 48.7% of the gene total number; （2） The pericancerous mucosa （P） and gastric cancer （T） were simultaneously compared with normal gastric mucosa, which had 71 genes with the same expression difference, of 61 genes were up-regulated （pericancerous SLR〉I.5）, and other 10 genes were down-regulated （pericancerous SLR〈 -1.5）. From their localization on the chromosome, there was simultaneously 71 genes appearance both in the pericancerous mucosa and in gastric cancer. The most one was 11 abnormal genes on the No. 19 chromosome. The next was No. 1, 2, 16 and 17 chromosomes which had 6 genes, respectively. It was not finding an abnormal gene on the No. 5, 14, 22 and Y chromosome. Conclusion： It suggested those genes may be related to the promotion in early gastric carcinogenesis and their progress. Four main groups （enzyme and enzyme regular, nucleic acid binding, signal transduction, protein binding） that associated gene＇s abnormality be played an importance role in studying the carcinogenesis of gastric cancer. The No. 19 and No. 1, 2, 16, 17 chromosomes are important sites of the oncogene transformation.     

Biological Significance and the Related Molecular Mechanism of Etsl mRNA Expression in Lung Cancer by Tissue Microarray （TMA）

Objective： To investigate the expressions and proteins in the pathogenesis, progression of lung molecular mechanism of Ets-1 mRNA, and TGFβ1 and c-Met cancer by tissue microarray （TMA） method. Methods： The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were detected in 89 primary lung cancers, 12 lung cancer with lymph-node metastasis and 12 precancerous lesions by FISH（fluorescence in situ hybridization） and immunohistochemical method, and 10 normal lung tissues were used as controls. Results： The expressions of Ets-1 rnRNA, and TGFβ1 and c-Met proteins were significantly higher in 89 primary lung cancer than in the control group （P〈0.05）. The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were related to lymph node metastasis and clinical stages. There was a positive correlation between the Ets-1 mRNA expression and TGFβ1 and c-Met proteins （P〈0.05）. Conclusion： Ets-1 mRNA, TGFβ1 and c-Met proteins may be related to the pathogenesis, progression and malignant behavior of lung cancer. They may play an important role in prognosis assessment of lung cancer.     

LGR5 is a promising biomarker for patients with stage Ⅰ and Ⅱ gastric cancer

Objective: To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) expressions in gastric cancer and to evaluate its clinical significance. Methods: LGR5 expression was assessed by immunohistochemistry in 257 gastric cancer patients after surgery. The relationships between LGR5 expression and clinicopathological features and patients prognosis were statistically analyzed. Results: The expression of LGR5 was significantly higher in gastric cancers as a cancer stem cell marker than in adjacent normal tissues (P<0.001), and more frequently in patients with intestinal type, well-moderate differentiation and stage Ⅰ and Ⅱ (P<0.05). Although we found gastric cancer patients with LGR5 positive expression had a poorer prognosis, it didn’t meet statistical significance (P>0.05). LGR5 negative expression was significantly related to the favorable overall survival in stage Ⅰ and Ⅱ gastric cancer patients (P<0.05). Furthermore, patients with high LGR5 expression tended to be more likely to get progression and have poorer progress-free survival (P<0.05). Multivariate Cox regression analysis revealed that LGR5 expression was an independent factor of overall survival for the patients with stage Ⅰ and Ⅱ gastric cancer (P<0.05). Conclusions: Our results show that LGR5 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of patients with stage Ⅰ and Ⅱ gastric cancer.     

Role of TGF-β1 and its Receptors in Breast Carcinogenesis:Evaluation of Gene Expression Patterns and Clinical Implications

OBJECTIVE Transforming growth factor β1 (TGF-β1) is a multifunc-tional cytokine that may play an important role in tumor development and progression. METHODS We evaluated gene expression patterns of TGF-β1 and its receptors [transforming growth factor β type I receptor (TβR-Ⅰ) and transforming growth factor β type II receptor (TβR-Ⅱ)] in tumor tissue from patients with breast cancer or with benign breast diseases (BBD) and adja-cent normal tissue from the patients with breast cancer. Included in the study were 527 breast cancer patients and 213 BBD patients who participated in the Shanghai Breast Cancer Study. RESULTS The expression levels of the TGF-β1, TβR-Ⅰand TβR-Ⅱ genes in breast tissue were quantified using real-time PCR. TβR-Ⅱ expres-sion in cancer tissue was decreased by over 50% as compared to either adjacent normal tissue from the same patients or benign tumor tissue from BBD patients (p<0.001). TGF-β1 expression was lower by approximately 20% in cancer tissue compared to adjacent normal tissue (p=0.14) or to be-nign tumor tissue (p=0.002). Although TβR-Ⅰ expression was also reduced in cancer tissue compared to adjacent normal tissue, or benign tumor tissue, the magnitude of the reduction was less apparent than that for TβR-Ⅱ. Compared to patients with the lowest tertile value for TβR-Ⅱ, patients with median tertile value for TβR-Ⅱ had more favorable overall survival (HR 0.47, 95% CI 0.27-0.85) and disease-free survival (HR 0.65, 95% CI 0.39-1.06). No apparent associations, however, were observed between TGF-β1 or TβR-Ⅰ expression and overall or disease-free survival. CONCLUSION The results from this study support the hypothesis that a decreased level of TβR-Ⅱ gene expression, and thus reduced TGF-β1 sensitivity, is related to breast tumor progression.     

Relationship between Microsatellite Alterations of RASSF1A Gene and Development of Cervical Carcinoma

Objective： To explore the relationship between microsatellite alterations of RASSFIA gene and the development of cervical carcinoma, and its relationship with HPV16 infection. Methods： Two sites of microsatellite polymorphism of RASSFIA gene were selected. Polymerase chain reaction （PCR） technique was used to detect LOH and MSI in 50 cases of cervical carcinoma and 40 cases of cervical intraepithelial neoplasia （CIN）, and to detect the infection state of HPV16. Results： At D3S1478 and D3S4604, the LOH rates of cervical carcinomas were 32.6% （14/43） and 48.9% （23/47）, the MSI rates were 14% （6/43） and 19.1% （9/47）, respectively. The LOH rates of CINs were 31.4% （11/35） and 39.5% （15/38）, the MSI rates were 11.4% （4/35） and 15.8% （6/38）, respectively. There were no significant differences between cervical carcinomas and CINs in respect to their positive rates of LOH and MSI at D3S1478 and D3S4604 （P〉0.05）. There were significant differences in LOH rates at D3S1478 and D3S4604 between the stage Ⅰ-Ⅱ and Ⅲ-Ⅳ cervical carcinomas and between the well/moderately differentiated cervical carcinomas and the poorly differentiated cervical carcinomas （P〈0.05）. The positive rates of LOH and MSI for CIN Ⅲ and noninvasive cervical carcinomas were higher than those in CIN Ⅰ-Ⅱ. The rates of infection of HPV16 in cervical cancer was obviously higher than that in CIN and in normal cervical tissues （P〈0.05）, and the incidence of LOH of RASSFIA gene was higher in HPV16（＋） than that in HPV16（-） （P〈0.05）. Conclusion： The RASSFIA gene change is a relatively late event in cervical carcinomas. The detection of LOH and MSI of RASSFIA gene might be helpful to the early diagnosis and the screening of cervical carcinoma. It might also be useful for predicting the prognosis of cervical carcinoma.     

Expression and clinical significance of REGγ in gastric cancer tissue and variously differentiated gastric cancer cell lines

OBJECTIVE To evaluate the REGγ expression in gastric cancer tissue and gastric cancer cell lines of various differentiation levels and its clinical significance. METHODS Immunohistochemistry was used to detect the expression of REGγ protein in 70 specimens of gastric cancer and 30 specimens of normal gastric mucosa. The relationship between the expression of REGγ protein and the biological behaviors of gastric cancer was analyzed. RT-PCR and Western blot were used to detect the mRNA level and the protein expression of REGγ in normal gastric cell line GES-1, well differentiated gastric cancer cell line MKN-28, moderately differentiated gastric cancer cell line SGC-7901 and poorly differentiated gastric cancer cell line BGC-823. RESULTS The expression rate of REGγ protein in gastric cancer tissue （52/70, 74.29%） was significantly higher than that in normal gastric tissue （12/30, 40%） （P 〈 0.01）. The expression rate of REGγ was correlated with tumor size （P 〈 0.01）, lymph node metastasis （P 〈 0.05）, differentiation degree （P 〈 0.01）, infiltration depth （P 〈 0.01） and distant metastasis （P 〈 0.05）. RT-PCR analysis showed that the expression of REGγ mRNA was 0.459 ± 0.079 in the normal gastric mucosa cell ling 0.588 ±0.118 in the well differentiated gastric cancer cell line, 0.715±0.066 in the moderately differentiated gastric cancer cell line, and 0.873 ± 0.099 in the poorly differentiated gastric cancer cell line, showing a negative correlation between REGγ mRNA expression and differentiation level （P 〈 0.05）. Western blot analysis showed that the expression of REGγ protein was 0.712±0.065 in the normal gastric mucosa cell line, 1.176±0.185 in the well differentiated gastric cancer cell line, 1.533 ± 0.127 in the moderately differentiated gastric cancer cell line, and 2.061± 0.398 in the poorly differentiated gastric cancer cell line, showing a negative correlation between REGγ protein expression and differentiation level （P 〈 0.05）. CONCLUSION REGγ is expressed in gastric cancer tissue and normal gastric tissue. In gastric cancer tissues, REGγ expression is positively correlated with the tumor size, lymph node metastasis, differentiation degree, infiltration depth and distant metastasis. Detecting the expression of REGγ mRNA and protein is helpful for early diagnosis and predicting prognosis of gastric cancer.     

Role of TGF-β1 and its Receptors in Breast Carcinogenesis： Evaluation of Gene Expression Pattems and Clinical Implications

OBJECTIVE Transforming growth factor β1 （TGF-β1） is a multifunc- tional cytokine that may play an important role in tumor development and progression. METHODS We evaluated gene expression patterns of TGF-β1 and its receptors [transforming growth factor β type Ⅰ receptor （TβR- Ⅰ ） and transforming growth factor β type Ⅱ receptor （TβR- Ⅱ ）] in tumor tissue from patients with breast cancer or with benign breast diseases （BBD） and adjacent normal tissue from the patients with breast cancer. Included in the study were 527 breast cancer patients and 213 BBD patients who participated in the Shanghai Breast Cancer Study. RESULTS The expression levels of the TGF-β1, TβR- Ⅰ and TβR-Ⅱ genes in breast tissue were quantified using real-time PCR. TIER- Ⅱ expression in cancer tissue was decreased by over 50% as compared to either adjacent normal tissue from the same patients or benign tumor tissue from BBD patients （p〈0.001）. TGF-β1 expression was lower by approximately 20% in cancer tissue compared to adjacent normal tissue （p=0.14） or to benign tumor tissue （p=0.002）. Although TβR-Ⅰ expression was also reduced in cancer tissue compared to adjacent normal tissue, or benign tumor tissue, the magnitude of the reduction was less apparent than that for TβR- Ⅱ. Compared to patients with the lowest tertile value for TβR- Ⅱ, patients with median tertile value for TβR- Ⅱ had more favorable overall survival （HR 0.47, 95% CI 0.27-0.85） and disease-free survival （HR 0.65, 95% CI 0.39-1.06）. No apparent associations, however, were observed between TGF-β1 or TβR- Ⅰ expression and overall or disease-free survival. CONCLUSION The results from this study support the hypothesis that a decreased level of TβR-Ⅱ gene expression, and thus reduced TGF-β1 sensitivity, is related to breast tumor progression.     

ANTIBODY TO ONCOGENE PROTEIN PRODUCT AND ITS CONJUGATE WITH RICIN A-CHAIN

The proteins encoded by oncogene were thought to be tumor associated antigen. The protein P110 in MGC803, a human gastric cancer cell line, was purified as immunogen. The IgY to the gastric cancer was extracted from eggs laid by immunized hen. The IgY could react immunohistochemically with gastric cancers. Positive staining rates of PAF were 80% in gastric cancers and markedly higher than in cancers of other organs and normal gastric tissue. The IgY-Ricin A was synthesized by the IgY conjugated with Ricin A- chain. TCID50 of MGC803 treated by the IgY-Ricin A was 0. 01 mg/ml and markedly lower than other cell. These results showed the IgY-Ricin A were able to react with gastric cancers selectively.     

Analysis of Metastatic-Related Gene Expression in Gastric Cancer by Low-Density cDNA Microarrays

OBJECTIVE To screen metastatic-related genes in human gastric cancer by a low-density cDNA microarray technique. METHODS A total of 18 paired gastric cancer and adjacent normal mu-cosa were examined by a low-density cDNA microarray containing 23 genes. RT-PCR was used for further verification. RESULTS The mRNA expression of MMP -7, heparanase, S100A4, hTERT, hRad17 in gastric cancers was higher than that in coupled normal mucosa (P=0.002, 0.00011, 0.000072, 0.002, 0.00016 respectively), whereas nm23H1, and CDH1 were lower (P=0.003, 0.012 respectively). The concordance was verified further by RT-PCR with a correlation coefficient of 0.774. In gastric primary lesions the mRNA expression of MMP-7, heparanase and S100A4 was higher in the serosa involved compared to non-involved (P=0.003, 0.009, 0.012 respectively), whereas nm23H1, CDH1, KAI1 were lower (P=0.001, 0.001, 0.006 respectively). With respect to the area of serosa involvement, MMP-7 and heparanase expressions were higher in an area of more than 20 cm2 compared to an area of less than 20 cm2 (P=0.001, 0.02 respectively), whereas nm23H1, CDH1 and KAI1 were lower (P=0.030, 0.041, 0.031 respectively). MMP-7 and hTERT expressions were higher in the heavier lymph node metastatic cases (no less than 7) than in the lighter lymph node metastatic cases (no more than 6, P=0.001, 0.005 respectively). CONCLUSION Expression of MMP -7, S100A4, heparanase, hTERT, KAI1, CDH1 and nm23H1 correlated closely with invasion and metastasis in gastric carcinomas. The low-density cDNA microarrays can be used to examine the expression of many genes simultaneously, parallely and quickly.