ABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of two tumor metastasis suppressor genes nm23 and KAI1 in gallbladder adenocarcinoma, and their clinicopathological significance.</p><p><b>METHODS</b>Specimens and clinical data from 31 gallbladder adenocarcinoma patients were collected. Histopathological grading and the expression of nm23 and KAI1 were detected by HE and immunohistochemical staining, respectively. All cases were followed up for at least three years.</p><p><b>RESULTS</b>Immunohistochemical staining showed that the positive rate of nm23 and KAI1 proteins was 71.0% (22/31) and 61.3% (19/31), respectively. The positive expression rates of nm23 and KAI1 proteins in the early stage carcinomas were significantly higher than those in the moderate and advanced stage ones (P exact = 0.0051 and P exact = 0.0084), and both had an negative correlation with clinicopathologic stage (P trend = 0.0047 and P trend = 0.0058). There was a significant difference in the expression of nm23 and KAI1 proteins among well, moderately and poorly differentiated carcinomas (P exact = 0.0328 and P exact = 0.0020). The expression of nm23 and KAI1 was positively correlated with histopathological grade (P trend = 0.0086 and P trend = 0.0006). There was also a significant difference in the expression of nm23 and KAI1 proteins between 17 survival and 14 dead patients (P exact = 0.0038 and P exact = 0.0001 ). A synergistic effect of nm23 and KAI1 protein on the survival was observed , and seemed to be more important than any individual gene alone (P exact = 0.0005).</p><p><b>CONCLUSION</b>The expressions of nm23 and KAI1 proteins are negatively correlated with clinical stage, but positively with histopathological grade in gallbladder adenocarcinoma. These two tumor metastasis suppressor genes may act synergistically to inhibit the tumor metastasis.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adenocarcinoma , Metabolism , Pathology , General Surgery , Cell Membrane , Metabolism , Cholecystectomy , Cytoplasm , Metabolism , Follow-Up Studies , Gallbladder Neoplasms , Metabolism , Pathology , General Surgery , Gene Expression Regulation, Neoplastic , Kangai-1 Protein , Metabolism , NM23 Nucleoside Diphosphate Kinases , Metabolism , Neoplasm Metastasis , Neoplasm Staging , Survival RateABSTRACT
<p><b>OBJECTIVE</b>To investigate the expressions of vascular endothelial growth factors (VEGF)-A, -C and -D and their prognostic significance and relation to angio- and lymphangiogenesis in gastric cancer.</p><p><b>METHODS</b>The expression of VEGF-A, -C and -D in 123 primary gastric cancers was detected by immunohistochemical staining. The lymphatic vessel density (LVD) and microvessel density (MVD) were assessed after immunohistochemical double-staining with D2-40 and CD34, respectively. The correlation between the expression of those VEGF factors and clinicopathological parameters were analyzed by univariate method. The overall survival was evaluated by Kaplan-Meier method and log-rank test. Multivariate analysis was carried out using Cox proportion hazard model.</p><p><b>RESULTS</b>The positive expression rate of VEGF-A, -C and -D in primary gastric cancer samples were 64.2%, 65.9% and 41.5%, respectively. High expression of VEGF-A, or -C or -D, or any two of them was correlated with high LVD (P < 0.05). High expression of both VEGF-A and -C was associated with high MVD, lymph node metastasis, LVI and MVI (P < 0.05). Both VEGF-C and -D high expression was correlated with LVI and lymph node metastasis (P < 0.05). The patients with high expression of these factors had a statistically shorter overall survival (P < 0.05). The patients with both VEGF-A and -C expression had the shortest survival (56 months). Multivariate analysis showed that VEGF-A high expression, MVD, lymph node metastasis and depth of tumor invasion were independent survival predictors (P = 0.033, 0.002, 0.019 and P < 0.001, respectively).</p><p><b>CONCLUSION</b>High expression of both VEGF-A and -C imply high potential of lymphangiogenesis, metastasis and poorer survival in gastric cancer patients. High expression of VEGF-C and -D may induce lymphangiogenesis and promote lymph node metastasis, but only VEGF-A is an independent predictor of survival.</p>