ERK蛋白磷酸化在局部晚期结肠癌的临床意义

Clinical Significance of ERK Phosphorylation in Locally Advanced Colon Carcinoma

目的:尽管MAPK通路异常活化在肿瘤发生、发展中发挥重要作用,但该通路在肿瘤特定阶段的具体作用尚缺乏研究。本文研究该通路活化在ⅢB期结肠癌的临床意义。方法:收集1997年1月至2002年5月中山大学肿瘤防治中心手术切除的ⅢB期结肠癌组织及其邻近的正常粘膜,采用免疫组织化学方法检测ERK蛋白磷酸化状态,分析其与临床病理特征以及5年生存率的关系。结果:p-ERK1/2蛋白出现于细胞浆和(或)细胞核。在56例ⅢB期结肠癌患者中,癌旁正常肠粘膜几乎无ERK蛋白磷酸化。与癌旁正常粘膜相比,26例(46.4%)癌组织处于ERK高磷酸化状态(P<0.001),29例(51.8%)癌组织的ERK磷酸化水平无变化,1例(1.8%)癌组织处于低磷酸化状态。ERK1/2蛋白磷酸化状态与ⅢB期患者年龄、性别、部位及病理分级无关。癌组织ERK高磷酸化患者的5年生存率较高。患者年龄、性别、部位及病理分级与生存率无相关性。结论:局部晚期结肠癌组织中MAPK通路可能不是控制肿瘤生物学行为的关键信号通路。

Objective According to previous studies, nveractivation of the MAPK （mitogen-activated protein kinase） pathway plays an important role in driving the progression of cancer and is correlated with the poor prognosis of colon cancer. However, there are few studies focusing on the effect of this overaetivation the MAPK pathway in different stages of tumor development. To specify the role of p-ERK in locally advanced colon cancer, we investigate the clinical significance of p- ERK1/2 in colon carcinomas of stage ⅢB, Methods： Data from 56 patients with colon carcinoma seen in our hospital between 1997 and 2002 were collected. We analyzed the carcinoma tissues and the corresponding adjacent mueosa. Phosphorylation of ERK1/2 was detected in the tissue sections with immunohistoehemistry. We used SPSS statistical analysis software to analyze the relationship among phosphorylation of ERK1/2, elinicopathologic charaeteristics, age, gender, tumor location, differentiation, and 5-year snrvival rate. Results： p-ERK1/2 was located in the eytoplasm and/or nucleus, p- ERK1/2 was almost absent in the tissues adjacent to colon cancer. Compared with normal mucosa, 26 （46.4%） carcinoma tissues showed a higher lever of phosphorylation of ERK1/2, 29 （51.8%） carcinoma tissues showed no difference, and only one case （1.7%） showed a lnwer phosphorylation level. The expression of p-ERK1/2 was not related to age, gender, tumor location or differentiation. Patients with higher phosphorylation levels of ERK1/2 showed a longer 5-year survival rate. Age, gender, differentiation and location were not coo＇elated with survival. Conclusion： The MAPK pathway may not play the most important role in controlling tire biological behavior of locally advanced colon carcinoma.