结肠癌中雌激素受体和衔接蛋白p66Shc的表达和意义

背景:雌激素和雌激素受体(ER)在结肠癌的发生、发展中起重要作用,然而ER在其中的具体作用机制尚不完全清楚。在甾类激素敏感性肿瘤细胞中,甾类激素可显著上调衔接蛋白p66Shc表达并刺激细胞增殖。目的:探讨ER和p66Shc在结肠癌中的表达特点及其临床意义。方法:以免疫组化方法检测65例石蜡包埋结肠癌组织及其癌旁非癌组织中的ER和p66Shc蛋白表达,分析p66Shc蛋白表达与结肠癌临床病理特征的相关性。结果:ER和p66Shc蛋白表达分别定位于细胞核和细胞质,结肠癌组织中的ER和p66Shc蛋白表达阳性率显著高于癌旁非癌组织(ER:47.7%对0%,P<0.01;p66Shc:49.2%对0%,P<0.01),且两者呈正相关(r=0.43,P<0.05)。p66Shc蛋白表达与结肠癌患者的性别、年龄以及原发肿瘤部位、肿瘤大小、大体类型、浸润深度、淋巴结转移、AJCC分期均无相关性,而与肿瘤组织学分级相关(高分化:22.2%,中分化:47.7%,低分化:75.0%,P=0.046)。结论:结肠癌可能是一种雌激素敏感性肿瘤。雌激素及其受体可能与p66Shc共同参与了结肠癌的发生、发展。

Expressions and Significance of Estrogen Receptor and Adaptor Protein p66Shc in Colon Cancer

Estrogen and estrogen receptor （ER） are considered to play important roles in the tumorigenesis and progression of colon cancer, however, the mechanism of ER in colon caner is still unclear. Adaptor protein p66Shc is upregulated by steroid hormones in hormone-sensitive cancer cells, which is correlated with the steroid hormone-stimulated cell proliferation. Aims： To investigate the expressions and significance of ER and p66Shc in colon cancer. Methods： Protein expressions of ER and p66Shc in 65 paraffin-embedded colon cancer tissue and the corresponding adjacent non- cancerous tissue were detected by immunohistochemistry. Correlation of p66Shc protein expression with the clinicopathological characteristics of colon cancer was analyzed. Results： Expressions of ER and p66Shc protein were located in nucleus and cytoplasm, respectively. Positivity rates of both ER and p66Shc protein were significantly higher in colon cancer tissue than in adjacent non-cancerous tissue （ER： 47.7% vs. 0%, P 〈0.01 ; p66Shc： 49.2% vs. 0%, P 〈0.01 ）. Moreover, positive correlation was found between ER and p66Shc protein expressions （r = 0.43, P 〈 0.05）. Expression of p66Shc protein had no correlation with gender, age, primary tumor location, tumor size, gross type, depth of tumor invasion, lymph node metastasis and AJCC stage, however, it was significantly correlated with histological grading of colon cancer （well differentiated： 22. 2%, moderately differentiated： 47. 7%, poorly differentiated： 75. 0%, P = 0.046）. Conclusions： Colon cancer might be an estrogen-sensitive malignancy. Estrogen and ER might cooperate with p66Shc to play a role in the tumorigenesis and progression of colon cancer.