Li Xiao-Han, Zheng Hua-Chuan, Wang Zhi-Gang, Takahashi Hiroyuki, Yang Xiang-Hong, Guan Yi-Fu, Takano Yasuo
Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Sugitani 2630, Toyama, Japan.
Anticancer Res. 2008 Mar-Apr;28(2A):1061-7.
MUC-1 is synthesized as a single polypeptide that then undergoes proteolytic cleavage, and is associated with the epidermal growth factor receptor tyrosine kinases. In malignancies, MUC-1 may function as an anti-adhesion molecule, but can also promote adhesion and presumably metastasis.
Expression of MUC-1, -2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas (n = 237) and adjacent non-cancerous mucosa specimens (n = 89) by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients.
MUC-1 was found to be highly expressed in gastric carcinomas in comparison with noncancerous mucosa (p < 0.05) and positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, UICC staging and MUC-4 expression (p < 0.05), but not with age, tumor size, MUC-2 or MUC-5AC expression (p > 0.05). Intestinal-type carcinomas showed more MUC-1 expression than their diffuse-type counterparts (p < 0.05). Kaplan-Meier analysis indicated that the cumulative survival rate of patients with no MUC-1 expression was significantly higher than those with weak, moderate or strong expression in gastric carcinomas (p < 0.05), but no difference was observed when tumors were stratified according to the depth of invasion (p > 0.05). Cox's analysis showed three independent prognostic factors, depth of invasion, lymphatic invasion and venous invasion, to affect the relationship between MUC-1 expression and prognosis.
Up-regulation of MUC-1 expression may be involved in pathogenesis, invasion, metastasis and differentiation of gastric carcinoma. Altered expression might therefore be employed as an indicator of pathobiological behavior of gastric carcinoma. MUC-1 expression was found to be a prognostic factor for gastric carcinoma patients, albeit not independent of parameters of invasion.
MUC-1最初作为单一多肽合成,随后经历蛋白水解切割,并与表皮生长因子受体酪氨酸激酶相关。在恶性肿瘤中,MUC-1可能作为一种抗粘附分子发挥作用,但也可促进粘附并可能促进转移。
通过免疫组织化学评估MUC-1、-2、-4和-5AC在胃癌组织芯片(n = 237)和相邻非癌黏膜标本(n = 89)中的表达,并与患者的临床病理参数和生存时间进行比较。
与非癌黏膜相比,MUC-1在胃癌中高表达(p < 0.05),且与浸润深度、淋巴管和静脉浸润、淋巴结转移、UICC分期及MUC-4表达呈正相关(p < 0.05),但与年龄、肿瘤大小、MUC-2或MUC-5AC表达无关(p > 0.05)。肠型癌比弥漫型癌显示出更多的MUC-1表达(p < 0.05)。Kaplan-Meier分析表明,在胃癌中,无MUC-1表达患者的累积生存率显著高于弱、中或强表达患者(p < 0.05),但根据浸润深度对肿瘤进行分层时未观察到差异(p > 0.05)。Cox分析显示,浸润深度、淋巴管浸润和静脉浸润这三个独立的预后因素影响MUC-1表达与预后之间的关系。
MUC-1表达上调可能参与胃癌的发病机制、浸润、转移和分化。因此,表达改变可作为胃癌病理生物学行为的一个指标。尽管MUC-1表达并非独立于浸润参数,但它是胃癌患者的一个预后因素。