【作者】 张宇龙；

【导师】 王凤安； 闫庆辉；

【作者基本信息】 河北医科大学 ， 外科学， 2008， 硕士

【摘要】 目的:进展期胃癌NF-κB及Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结癌细胞再表达的关系及其临床意义,探讨NF-κB、Rb蛋白与E-cadherin/catenin复合物对胃癌转移机制和对患者预后的影响。寻求在分子水平对胃癌早期诊断和治疗更新、更有效的方法。方法:用采用免疫组化过氧化物酶标记链霉卵白素法(SP)分别检测了NF-κB、Rb蛋白在肿瘤原发灶与E-cadherin/catenin复合物在86例进展期胃癌原发灶及其相应淋巴结内癌细胞的表达情况,并结合肿瘤的大小、浸润深度、分化程度、组织学类型、淋巴结转移和患者的预后等临床病理因素进行综合分析。结果:NF-κB、Rb蛋白与E-cadherin/catenin复合物免疫阳性产物均为棕黄色,NF-κB、Rb染色定位于细胞浆或细胞核,E-cadherin、α-、β-及γ-catenin染色定位于细胞膜。NF-κB蛋白在86例进展期胃癌组织中表达阳性率达81.40% (70/86),Rb蛋白在86例进展期胃癌组织中表达阳性率达65.12% (56/86),E-cadherin/catenin复合物在肿瘤原发灶只有1例正常表达,85例不正常表达,异常表达率为98.84%,该复合物在转移淋巴结内癌细胞中再表达阳性率为63.95%(55/86)。NF-κB的表达与肿瘤细胞的病理类型(印戒细胞癌、未分化癌、磷癌及腺磷癌因样本含量过小,故未予统计)密切相关,在管状腺癌中阳性表达率为85.96% (49/57),在粘液腺癌中阳性表达率为61.90% (13/21),差异显著(P < 0.05);NF-κB的表达与肿瘤细胞的分化程度密切相关,在中高分化胃癌中的表达阳性率为91.43% (32/35),在低分化胃癌中的表达阳性率为74.51% (38/51),差异显著(P < 0.05);NF-κB的表达与肿瘤大小及肿瘤浸润深度无关,在直径大于5cm的肿瘤中阳性表达率为83.08% (54/65),在直径小于5cm从肿瘤中阳性表达率为76.19% (16/21),差异无显著性(P > 0.05);在浸润深度侵及浆膜层的肿瘤中阳性表达率为82.05% (64/78),在浸润深度未侵及浆膜层的肿瘤中阳性表达率为75.00% (6/8),差异无显著性(P > 0.05)。Rb蛋白的表达与肿瘤细胞的分化程度密切相关,在中高分化胃癌中的表达阳性率为85.71% (30/35),在低分化胃癌中的表达阳性率为50.98% (26/51),差异显著(P < 0.05);Rb蛋白的表达与肿瘤细胞的病理类型(印戒细胞癌、未分化癌、磷癌及腺磷癌因样本含量过小,故未予统计)无关,在管状腺癌中阳性表达率为70.18% (40/57),在粘液腺癌中阳性表达率为71.43% (15/21),差异无显著性(P > 0.05);Rb蛋白的表达与肿瘤大小及肿瘤浸润深度无关,在直径大于5cm的肿瘤中阳性表达率为60.00% (39/65),在直径小于5cm从肿瘤中阳性表达率为80.95% (17/21),差异无显著性(P > 0.05);在浸润深度侵及浆膜层的肿瘤中阳性表达率为74.36% (50/78),在浸润深度未侵及浆膜层的肿瘤中阳性表达率为75.00% (6/8),差异无显著性(P > 0.05)。E-cadherin/catenin复合物在转移淋巴结癌细胞中的再表达与肿瘤细胞的分化程度密切相关,在中高分化胃癌中的表达阳性率为77.14% (27/35),在低分化胃癌中的表达阳性率为54.90% (28/51),差异显著(P < 0.05);E-cadherin/catenin复合物在转移淋巴结癌细胞中的再表达与肿瘤细胞的病理类型(印戒细胞癌、未分化癌、磷癌及腺磷癌因样本含量过小,故未予统计)无关,在管状腺癌中阳性表达率为73.68% (42/57),在粘液腺癌中阳性表达率为52.38% (11/21),差异无显著性(P > 0.05);E-cadherin/catenin复合物在转移淋巴结癌细胞中的再表达与肿瘤大小及肿瘤浸润深度无关,在直径大于5cm的肿瘤中阳性表达率为64.62% (42/65),在直径小于5cm从肿瘤中阳性表达率为61.90% (13/21),差异无显著性(P > 0.05);在浸润深度侵及浆膜层的肿瘤中阳性表达率为74.36% (50/78),在浸润深度未侵及浆膜层的肿瘤中阳性表达率为62.50% (5/8),差异无显著性(P > 0.05)(见表2)。Kaplan-Meier曲线显示NF-κB、Rb蛋白的表达与患者的预后无关(P > 0.05)(见图1、2);E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达情况与患者的预后密切相关(P < 0.05)(见图3)。Wilcoxon’s log-rank test进行组间差别检验显示各组间差别无显著性(P > 0.05)(见表3)。Cox’s proportional-hazard多变量分析显示E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达可以作为一个独立的预后因素(P < 0.05)(见表4)。Spearman秩相关分析显示NF-κB、Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达均无显著相关性(见表5、6、7)。结论:NF-κB、Rb蛋白与E-cadherin/catenin复合物可能与胃癌的发生、发展和转移密切相关;胃癌中存在NF-κB、Rb蛋白的高表达,转移淋巴结癌细胞中存在E-cadherin/catenin复合物的高再表达;E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达情况与患者的预后密切相关,可以作为一个独立的预后因素,NF-κB、Rb蛋白的表达与预后无关;NF-κB、Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达三者间无显著相关性。临床可以通过检测NF-κB、Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达提高早期诊断和早期治疗的敏感性并改善预后。更多还原

【Abstract】 Objective: The aim of this study was to study the expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes from advanced gastric carcinoma,and to evaluate its clinical significance,to investigate the unite factor effect of NF-κB, Rb and E-cadherin/catenin complex for metastatic mechanism of gastric carcinoma and prognosis. Therefore , to look for a kind of more sensitive and reliable method for early period diagnosis and early period remedy in a molecule level of gastric carcinoma.Methods: S-P immunohistochemical technique was used to examine the expression of NF-κB, Rb in primary advanced gastric carcinoma and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes from 86 advanced gastric carcinoma. The level of the expression was analyzed combined with clinicopathological features of the size of the tumor, infiltration depth, pathological differentiation, tumor pathological stages, lymph node metastasis and prognosis. Results: The color of the immune positive products of NF-κB,Rb was buffy and located in cytoplasm or nucleus and E-cadherin/catenin complex was buffy and located in plasmalemma. The rate of positive expression of NF-κB was 81.40% (70/86) in primary advanced gastric carcinoma. The rate of positive expression of Rb was 65.12% (56/86) in primary advanced gastric carcinoma. The rate of positive re-expression of E-cadherin/catenin complex was 63.95% (55/86) in cancerous cells of metastatic lymph nodes from advanced gastric carcinoma. The expression of NF-κB was lower in mucinous adenocarcinoma than those in adencarcinoma and the rate of positive expression was 61.90% (13/21) and 85.96% (49/57) respectively (P < 0.05). The expression of NF-κB was lower in poor differentiation degree than those in high and moderate differentiation degree and the rate of positive expression was 74.51% (38/51) and 91.43% (32/35) respectively (P < 0.05). The expression of NF-κB was not remarkable difference in the diameter in the primary advanced gastric carcinoma and the rate of positive expression was 83.08% (54/65) and 76.19% (16/21) respectively (P > 0.05). The expression of NF-κB was not remarkable difference in the infiltrated range limited to muscle stratum than serosa stratum and the rate of positive expression was 82.05% (64/78) and 75.00% (6/8) respectively (P > 0.05). The expression of Rb was lower in poor differentiation degree than those in high and moderate differentiation degree and the rate of positive expression was 74.51% (38/51) and 85.71% (30/35) respectively (P < 0.05). The expression of Rb was not remarkable difference in the mucinous adenocarcinoma than those in adencarcinoma and the rate of positive expression was 70.18% (40/57) and 71.43% (15/21) respectively (P > 0.05). The expression of Rb was not remarkable difference in the diameter in the primary advanced gastric carcinoma and the rate of positive expression was 60.00% (39/65) and 80.95% (17/21) respectively (P > 0.05). The expression of Rb was not remarkable difference in the infiltrated range limited to muscle stratum than serosa stratum and the rate of positive expression was 74.36% (50/78) and 75.00% (6/8) respectively (P > 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was lower in poor differentiation degree than those in high and moderate differentiation degree and the rate of positive expression was 54.90% (28/51) and 77.14% (27/35) respectively (P < 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not remarkable difference in the mucinous adenocarcinoma than those in adencarcinoma and the rate of positive expression was 52.38% (11/21) and 73.68% (42/57) respectively (P > 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not remarkable difference in the diameter in the primary advanced gastric carcinoma and the rate of positive expression was 64.62% (42/65) and 61.90% (13/21) respectively (P > 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not remarkable difference in the infiltrated range limited to muscle stratum than serosa stratum and the rate of positive expression was 74.36% (50/78) and 62.50% (5/8) respectively. There is no remarkable difference between the groups by Wilcoxon’s log-rank test. And the Cox’s proportional-hazard show that the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was a independent factor of prognosis. The expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not significant correlated among each (P > 0.05).Conclusion: NF-κB, Rb and E-cadherin/catenin complex may be closely correlated to the occurrence, the advancement and the metastasis of gastric carcinoma. The expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was increased from advanced gastric carcinoma. The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was closely correlated and could be a independent factor of prognosis. The expression of NF-κB, Rb was not correlated to the prognosis. The expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not significant correlated among each. Therefore, NF-κB, Rb and E-cadherin/catenin complex could be checked to enhance the sensitivity of diagnosis and remedy early period and to improve the prognosis.更多还原