| Objective:Fascin is an actin-bundling protein expressed in many human carcinomas, although absent from most normal epithelia. Fascin plays a key role in the assembly and stability of cell protrusions and other actin-based structures. In carcinoma cells, it can promote filopodia and invadopodia formation, and then promote cells migration and invasion. Recent clinical studies showed that fascin is up-regulated in some epithelial carcinomas and correlates with unfavorable prognosis. Fascin is an interesting candidate biomarker for aggressive, metastatic carcinoma, but the expression of fascin in human gallbladder carcinoma has not yet been studied systematically. This study was to evaluate the expression of fascin in gallbladder carcinoma, and to analyze its correlation with clinicopathologic features and prognosis of gallbladder carcinoma.Methods:The clinicopathologic features of67cases of gallbladder carcinoma were collected. We evaluated the expression of fascin by immunohistochemistry in the paraffin sections of these67cases of gallbladder carcinoma,20gallbladder adenomatoid polypus tissues and20normal gallbladder epithelial tissues. Positive immunoreactivity was defined as stained more than5%of the total number of cells. The correlation between fascin expression and clinicopathologic parameters and prognosis of the tumor was analyzed.Results:In67patients,39cases were found with positive fascin immunoreactivity (58.2%),18cases of the patients were classified as "+"(26.9%), and21cases were classified as "++"(31.3%). Furthermore, to investigating the correlations between fascin expression and the clinicopathologic parameters, we found that fascin expression was positively correlated with serosal invasion, lymphatic metastasis and TNM staging of the gallbladder carcinoma (P<0.05). Fascin expression had no association with gender, age, cholelithiasis, M stage, histology type and tumor grade (P>0.05). The overall median disease-specific survival time (DSS) was32months (5-year survival rate,20.90%). The DSS of fascin-negative patients was significantly better than that of fascin-positive patients (median DSS,45months vs19months, X~2=27.301, P<0.001). Furthermore, in fascin-positive group, the DSS of the sub-group with fascin "+" expression was significantly better than that of fascin "++" expression sub-group (median DSS,28months vs17months,X~2=13.579, P<0.001).Conclusion:There is no expression of fascin in normal gallbladder epithelium or adenomatoid polypus tissues, but the expression of fascin was positive in part cases of gallbladder carcinoma, which indicated that the change of skeleton of gallbladder carcinoma cells. Fascin expression correlates with serosal invasion, lymphatic metastasis and TNM staging of the gallbladder carcinoma. Over-expression of fascin might play an important role in invasiveness and metastasis of gallbladder carcinoma. The patients with fascin over-expression have a poor prognosis; fascin can be used as a prognostic marker and a new target for the treatment of gallbladder carcinoma. Objective:To investigate the lymph node metastasis patterns of gallbladder cancer (GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor.Methods:From May1995to December2010, a total of78consecutive patients with GBC underwent a radical resection at Liaocheng People’s Hospital. A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder. Demographic, operative and pathologic data were recorded. The lymph nodes retrieved were examined histologically for metastases routinely from each node. The positive lymph node count (PLNC) as well as the total lymph node count (TLNC) was recorded for each patient. Then the metastatic to examined lymph nodes ratio (LNR) was calculated. Disease-specific survival (DSS) and predictors of outcome were analyzed.Results:With a median follow-up time of26.50mo (range,2-132mo), median DSS was29.00±3.92mo (5-year survival rate,20.51%). Nodal disease was found in37patients (47.44%). DSS of node-negative patients was significantly better than that of node-positive patients ((median DSS,40mo vs17mo, X~2=14.814, P<0.001), while there was no significant difference between pNl patients and pN2patients (median DSS,18mo vs13mo,X~2=0.741, P=0.389). Optimal TLNC was determined to be four. When node-negative patients were divided according to TLNC, there was no difference in DSS between TLNC<4subgroup and TLNC≥4subgroup (median DSS,37mo vs54mo, X~2=0.715, P=0.398). For node-positive patients, DSS of TLNC<4subgroup was worse than that of TLNC≥4subgroup (median DSS,13mo vs21mo,X~2=11.035, P<0.001). Moreover, for node-positive patients, a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into2separate survival groups (<6orz≥6, respectively; median DSS,15mo vs33mo, X~2=11.820, P<0.001). DSS progressively worsened with increasing PLNC and LNR, but no definite cut-off value could be identified. Multivariate analysis revealed histological grade, TNM staging, TLNC and LNR to be independent predictors of DSS. Neither location of positive lymph nodes nor PLNC were identified as an independent variable by multivariate analysis.Conclusion:Both TLNC and LNR are strong predictors of outcome after curative resection for GBC. The retrieval and examination of at least6nodes can influence staging quality and DSS, especially in node-positive patients. |
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