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<p><b>OBJECTIVE</b>To investigate the association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma.</p><p><b>METHODS</b>Clinicopathological data of 240 patients with gastric adenocarcinomas were retrospectively analyzed. The expression of chromogranin A, synaptophysin and secrectagogin in cancer tissue was assessed by immunohistochemistry. The association of neuoroendocrine differentiation parameters with disease progression and survival of patients was analyzed.</p><p><b>RESULTS</b>The expression of synaptophysin was positively correlated with depth of invasion and secretagogin more often expressed in cases with lymph node metastasis. In Lauren diffuse type of cancer, expression of chromogranin A and secretagogin was unfavorable prognostic predictor. In TNM stage II adenocarcinoma, expression of chromogranin A and synaptophysin related to poor survival, and multivariate Cox proportional hazard model showed that synaptophysin was an independent predictor for poor survival.</p><p><b>CONCLUSION</b>Neuroendocrine differentiation predicts deeper depth of invasion, more possibility of lymph node metastasis and poor survival in gastric adenocarcinoma.</p>
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Humanos , Adenocarcinoma , Diagnóstico , Patologia , Biomarcadores Tumorais , Metabolismo , Cromogranina A , Metabolismo , Progressão da Doença , Imuno-Histoquímica , Metástase Linfática , Estadiamento de Neoplasias , Tumores Neuroendócrinos , Diagnóstico , Patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Secretagoginas , Metabolismo , Neoplasias Gástricas , Diagnóstico , Patologia , Sinaptofisina , MetabolismoRESUMO
Objective To study Twist,E-CD expression in colorectal cancer tissues and its relationship with colorectal cancer invasion,metastasis and prognosis.Methods Immunohistochemical staining (EnVision) was used to detect E-CD,Twist expression of normal colon mucosa in 30 cases,colorectal adenoma in 30 cases and colorectal cancer tissues in 142 cases.Chi-square、Fisher's and Spearman test were used to analyze E-CD and Twist protein expression,Kaplan-Meier survival analysis and multivariate COX regression were used to analyze prognosis of patients.Results E-CD in the normal mucosa were positively expressed in 90% cases,which was significantly higher than that in colorectal adenomas (63%) (P =0.046) and colorectal cancer tissues (42%) (P =0.000).E-CD expression was related to tumor differentiation (P =0.048),invasion depth (P =0.000),vein (P =0.000) and lymph vessel invasions (P =0.030),lymph node metastasis (P =0.001) and Dukes' stage (P =0.016),but not related to patient's age(P =0.174),gender(P =0.159),tumor size (P =0.628) and tumor histological type (P =0.153).1,3,5 year survival rate in patients with positive E-CD expression was significantly higher than that in patients with negative expression (P =0.000).Positive expression rate of Twist in colorectal cancer tissues (68%) was significantly higher than that in normal mucosa (20%,P =0.000) and colorectal adenomas (30%,P =0.000).Twist expression was related to tumor histological type (P =0.000),differentiation(P =0.000),invasion depth(P =0.000),vein(P =0.000) and lymph vessel invasions(P =0.000),lymph node metastasis(P =0.010) and Dukes' stage(P =0.000).1,3,5 year's survival rate of Twist-negative expression patients was significantly higher than that in patients with positive expression (P =0.000).E-CD and Twist in colorectal cancer tissues were negatively correlated (r =-0.530,P =0.000).COX multivariate analysis shows that vein invasion (P =0.045),lymph node metastasis (P =0.040),Dukes' stage (P =0.000),E-CD (P =0.003) and Twist (P =0.031) were independent prognostic indicators.Conclusions E-CD and Twist expression in colorectal cancer are related to tumor invasion,metastasis and prognosis.Low E-CD expression and high Twist expression are related to poor prognosis of colorectal cancer patients.
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Objective To explore the expression and clinical significance of Twist. E-cadherin and N-cadherin in gallbladder carcinoma. Methods From 2000 to 2008, in Zhejiang Provincial People's Hospital, the expression of Twist, E-cadherin and N-cadherin protein were detected in 79 surgically removed gallbladder carcinoma tissue specimens in paraffin blocks and 20 normal gallbladder tissue specimens by tissue microarray technique and immunohistochemistry. Results Compared with normal gallbladder tissues, the expression of Twist and N-cadherin was up-regulated in gallbladder carcinoma tissues and the positive percentage was 68.3% and 49.4% respectively, while which both were 1/20 in normal gallbladder tissues. The percentage of high E-cadherin expression in gallbladder carcinoma tissues was only 27.8 %, which was significantly lower than that in normal gallbladder tissues (20/20;X2 =29.31, P<0. 05). The expression of Twist was correlated with T classification, lymph node metastasis, distant organ metastasis, hepatoduodenal ligament invasion, lymphatic invasion and UICC stage of gallbladder carcinoma (P<0.05). The expression of E-cadherin was correlated with T classification, distant organ metastasis, hepatoduodenal ligament invasion, differentiation degree and UICC stage of gallbladder carcinoma (P<0.05). The expression of N-cadherin was only correlated with lymphatic invasion of gallbladder carcinoma (P <0.05 ). There was significant negative correlation between Twist and E-cadherin expression (P<0. 01). All the 79 gallbladder carcinoma patients were followed up after the surgery, the mean follow-up time was 30.6±14.3months. The 3-year survival rates of patients with low or high Twist expressions were 66% and 7% respectively,there was significant difference between the two groups(P<0. 01). The 3-year survival rates of patients with low or high E-cadherin expressions were 25 % and 86 % respectively, the difference of two groups was significant(P<0.01). The 3-year survival rates of patients with low or high Ncadherin expressions were 39% and 41% respectively, there was no significant difference between the two groups(P>0.05). The multivariate analysis indicated that the Twist expression was one of independent prognostic factors of gallbladder carcinoma. Conclusion The abnormal expression of Twist and E-cadherin was correlated with the development and progression of gallbladder carcinoma,and Twist expression was one of the independent prognostic factors of gallbladder carcinoma.
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Objective To predict the secondary structure and the B cell epitopes of human heparanase protein, and to identify its immunogenicity. Methods The flexible regions of secondary structure and the B cell epitopes of human heparanase amino acid sequence were predicted by DNAStar and Bcepred software. The multiple antigenic peptides (MAP) of the epitopes were synthesized in 8-branch form. Rabbits were immunized with the 8-branch MAPs mixed with a universal T-helper epitope human IL-1β peptide (VQGEESNDK, amino acid 163-171 ). The immunogenicity of the synthesized peptides was evaluated by ELISA, Western blot and immunohistochemistry. Results Amino acid 1 -15 ( MAP1), 279-293 (MAP2) and 175-189(MAP3) of large-subunit of human heparanase protein was predicted as the most potential epitopes of human heparanase protein. All the three synthesized MAPs induced high titer of antibodies. ELISA, Western blot and immunohistochemistry analysis showed all the three MAPs could produce high titer serum antibodies, antibodies induced by MAP1 and MAP2 had high specific binding activity , and MAP2 antibody showed the strongest binding activity with liver cancer tissues. Conclusion The large-subunit No. 1-15, 279-293 amino acid of human heparanase protein may be the B cell preponderant epitopes and the strongest immunogenicity may be No. 279-293 peptide, which provided a theoretic basis for the antibody and vaccine development of heparanase subunit peptide.
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potential use in clinical therapy and prognosis estimation of the tumor.
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<p><b>OBJECTIVE</b>To make quantitative analysis of DNA content of breast cancer with neuroendocrine (NE) cells and its significance.</p><p><b>METHODS</b>Using MIPS-III image analyzer, DNA content and 9 parameter measurements of the tumor nuclei were made in both NE positive (17) and negative (64) breast carcinomas.</p><p><b>RESULTS</b>Out of 81 breast carcinomas, 17 cases were NE positive while 64 cases were NE negative. In the NE (+) cases, the integral optic density, mean optic density, DNA index, DNA stemlines peak, > 5c aneuploidy cells and the rate of aneuploidy cells were all lower than those in the NE negative breast carcinoma cases (P < 0.01). The positive rates of NE cells were 32.5% and 7.9% in grade I - II breast carcinomas and in grade III breast carcinomas respectively with significant difference between the two groups (P < 0.01).</p><p><b>CONCLUSION</b>Our study shows that NE (+) breast carcinomas have lower DNA parameters than NE (-) breast carcinomas, suggesting that NE (+) breast carcinomas have lower malignancy.</p>
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Aneuploidia , Neoplasias da Mama , Genética , Patologia , Carcinoma Neuroendócrino , Genética , Patologia , DNA de Neoplasias , Genética , MetabolismoRESUMO
Objective To study the expression of cyclin E and epidermal growth factor receptor (EGFR) in breast carcinoma and their correlation with metastasis,relapse and survival time. [WT5”HZ]Methods Cyclin E and EGFR expressions at protein level were determined by immunohistochemistry technique in 110 patients with breast carcinoma. Results Of the 110 patients,cyclin E and EGFR positive expression were both in 60 (54.55%),and there was a positive relationship between cyclin E and EGFR expression (r s=0.823,P =0.001);Cyclin E and EGFR expression level were correlated with clinical stage (? 2=12.86,P =0.005;? 2=14.21,P =0.004),tumor histological grading (? 2=8.86,P =0.005;? 2=4.90,P =0.04),lymph node metastasis (? 2=10.22,P =0.001;? 2=9.62,P =0.002),ER expression (? 2=29.8,P =0.001;? 2=32.08,P =0.001) and PR expression (? 2=19.56,P =0.001;? 2=26.92,P =0.001). The rate of local relapse and distant metastasis in cases with positive cyclin E and EGFR expression were significantly higher than that in cases with negative expression (? 2=7.33,P =0.01;? 2=7.88,P =0.005);The mean survival time and 5-year survival rate in cases with positive cyclin E and EGFR was significantly shorter than that in cases with negative expression. [WT5”HZ]ConclusionCyclin E and EGFR expression can predict the relapse and metastasis of breast carcinoma. They can be used as markers of prognosis of breast carcinoma in clinical practice.
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Objective To investigate the expression of heparanase and vascular endothelial growth factor-C (VEGF-C) protein in human gastric carcinoma, and to evaluate its clinical implications during the progress of gastric carcinoma. Methods The expression of heparanase and VEGF-C protein in 97 cases of gastric cancer, adjacent tissues and normal tissues in 20 subjects was determined by immuno- histochemistry. Results The positive rate of heparanase and VEGF-C protein in tumor tissues (61.9% and 66.0%) were significantly higher than those in adjacent tissues of cancer (7.2% and 5.0%) and normal tissues (8.3% and 5.0%, P 0.05) . The positive expression of VEGF-C protein in the tumor tissues was significantly related with serosal infiltration, lymphatic invasion, lymph node metastasis and TNM stage Ⅲ-Ⅳ (P0.05). The 1, 3 and 5-year survival rates of patients with expression of heparanase or VEGF-C protein were significantly less than that of patients without expression of heparanase or VEGF-C (P
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0.05). Conclusions Peroperative transcatheter arterial infusion chemotherapy resulting in apoptosis of adenocarnoma, can raise the radical operation rate, and prolong survival rate for colprectal carcinoma patients.
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Purpose:To study the expressions of cyclin E and P53 in gastric carcinoma in relation to biological behavior and prognosis.Methods:Cyclin E and P53 expressions at protein level were determined by immunohistochemistry technique in 128 patients with gastric carcinoma.Results:Of the 128 patients , cyclin E positive expression was in 57(44 5%),P53 positive expression was in 67(52.3%),P53 and cyclin E were both positive in 48(37.5%),respectively.Cyclin E and P53 expression level were correlated with tumor size , invasion depth, regional lymph node status, vessel invasion, and distant metastasis, Univariate analysis demonstrated better survival in patients with negative cyclin E and P53 expressions than those with positive expression. By COX multivariate analysis, cyclin E expression level was found to be of independent prognostic significance, however p53 expression level was not found to be of independent prognostic significance.Conclusions:Cyclin E expression within gastric carcinoma tissues is an indicator of tumor behavior and prognosis, p53 expression within gastric carcinoma tissue is only an indicator of tumor behavior. [
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AIM:To screen the gene expression profiles of normal gastric mucosa,primary gastric cancer and metastatic lymph nodes by gene expression microarray and the associated genes with lymph node metastasis by bioinformatics. METHODS:The differentially expressed genes of nontumorous gastric mucosa (group A),primary gastric cancer (group B) and metastatic lymph nodes (group C) were screened by gene expression microarray obtained from Affymetrix company. The results were further analyzed by bioinformatic software including Gene Expression Profiles Analysis of Cohort Experiment,Gene Ontology Enrichment Analysis and Pathway Significant Analysis. The expression of TLN1 in group A,B and C were confirmed by real-time reverse transcription PCR. RESULTS:278 genes were persistent up-regulated in group A,B,C,which participated mainly in immunologic responses,cell adhesion,phosphate transport,inorganic anion transport,cell chemotaxis,cell motility and signal transduction. While 387 genes were persistent down-regulated in group A,B,C,which were concerned with digestion,glucide metabolism,lipid metabolism,protein metabolism,one-carbon compound metabolism,nitrogen compound catabolism and cell adhesion. The pathway analysis suggested that integrin-mediated cell adhesion pathway were abnormally regulated. These genes including THBS1,TLN,CAPN3,ITGAX,SORBS1,CAPN6,CAPN9 were continuous up-regulated or down-regulated in integrin-mediated cell adhesion pathway. The expressions of TLN1 in group A,B,C were 0.0000342?0.0000711,0.1064?0.1251 and 0.2886?0.3529,respectively. The expression of TLN1 in metastatic lymph nodes was significantly higher than that in nontumorous gastric mucosa and primary gastric cancer (P
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Objective To investigate the mRNA expression of UPA and MMP-9 in gastric carcinoma and their correlation with histological type, growth-type, differentiation, vessel invasion, metastasis and prognosis. MethodsIn situ hybridization was used to detect the mRNA expression of UPA and MMP-9. ResultsIn situ hybridization revealed that among 105 cases, the positive rates of UPA mRNA and MMP-9 mRNA were both 58.1%. There was no significant relationship between UPA mRNA and histological type( r _ s = 0.123, P =0.210)and differentiation ( r _ s =0.102, P =0.298)of the tumor. However, there was a significant difference between growth-type( r _ s =0.344, P =0.001),tumor invasion depth( r _ s =0.296, P =0.002),vessel invasion( r _ s =0.198, P =0.042),lymph node( r _ s =0.332, P =0.001)and distant metastasis( r _ s =0.530, P =0.001);there was no significant relationship between MMP-9 mRNA staining and histological type( r _ s =0.143, P =0.145)and differentiation( r _ s =0.102, P =0.298)of the tumor. However, there was a statistically significant difference between growth-type( r _ s =0.267, P =0.006),tumor invasion depth ( r _ s =0.335, P =0.001)、vessel invasion( r _ s =0.209, P =0.032),lymph node( r _ s =0.343, P =0.001)and distant metastasis( r _ s =0.468, P =0.001);There was a positive relationship between UPA mRNA and MMP-9 mRNA expression( r _ s =0.237, P =0.015). The mean survival time in cases with positive UPA mRNA and MMP-9 mRNA expression were significantly shorter than that of cases with negative expression. ConclusionThe mRNA expression of UPA and MMP-9 can predict the invasion and metastasis of gastric carcinoma, They can be used as markers of prognosis of gastric carcinoma in clinical practice.