MUC1与β-catenin协同异常表达对胃癌细胞增殖的影响

Proliferating regulation of gastric cancer by coexisting aberrant MUC1 and β-catenin expression

目的探讨胃癌中MUC1与β-catenin异常表达的意义及其与胃癌临床分期、组织学类型、肿瘤发生部位、肿瘤大小和核分裂指数等临床病理学关系。方法收集外科胃癌手术切除标本61例,应用HE染色切片进行组织病理学分类与核分裂指数评价,EnVision两步法行MUC1与β-catenin单克隆抗体免疫组织化学染色,10%以上肿瘤细胞出现胞浆聚集及细胞核着色被视为异常表达。结果本组胃癌中32例(52.46%)有MUC1异常表达,29例(47.54%)有β-catenin异常表达,MUC1与β-catenin异常表达一致率为73.77%。MUC1异常表达组核分裂指数增加(P=0.027),肿瘤在胃底贲门部相对好发(P=0.068)。MUC1或β-catenin单项异常表达与其它临床病理学指标无明显关系。MUC1与β-catenin共同异常表达时核分裂指数增高较MUC1单项异常表达以及MUC1与β-catenin无异常表达组更加明显(P=0.004)。结论β-catenin的异常表达表明部分胃癌出现Wnt/β-catenin信号通道异常活化。MUC1通过Wnt信号通道辅助活化因子作用促进β-catenin对胃癌细胞增殖的调控,两者共同异常表达明显促进胃癌细胞增殖;MUC1与β-catenin可作为反映胃癌生物学行为的有用标记。

Objective To study the significance of aberrant expression of MUC1 and 1β-catenin in gastric cancer and the relationship with clinicopathological paremeters including histological classification, TNM stage, location, tumor size and mitosis index. Methods A total of 61 eases of resected gastric cancer samples were collected. The high sensitive EnVision two steps immunohistochemical method had been used to detect the aberrant expression of M UCI and β-catenin on gastric cancer tissues, Over 10 percent of cancer cells with nuclear staining was considered as aberrant expression. Mitosis index and histological classification were evaluated based on H＆E staining. Results Thirty-two out of 61 cases（52.46% ） showed aberrant MUC1 expression. Twenty-nine out of 61 cases（47,54%） showed aberrant β-catenin expression. The concordance rate of M UC1 and β-catenin aberrant expression was 73.77%. Gastric cancer with M UC1 aberrant expression showed higher mitosis index compared to no-MUC1 aberrant expression group（ P = 0.027）. The tumor disclosed the trend of upper-stomach location（P = 0.68）. The coexisting of M UCI and β-catenin aberrant expression closely related with high mitosis index（ P = 0.004）, but no statistic significance was found between M UC1 and β-catenin aberrant expression with other clinicopathological parameters including age, gender, location, Borrmann＇s types, tumor size, lymph node metastasis, Lauren＇s classification as well as TNM stage. Conclusion There is aberrant activation of Wnt/β-catenin signal transduction pathway in a portion of gastric cancer, MUG1 involves in proliferating regulation in gastric cancer as a coactivation factor. MUG1 and β- catenin can be used as markers for evaluating biologic behavior in gastric cancer.