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目的探讨p-mTOR在Luminal A型与Luminal B型乳腺癌中表达情况的差异,并全面系统分析该蛋白表达与临床病理特征的关系及对预后的影响。方法选取1999年1月至2008年12月间于北京协和医学院中国医学科学院肿瘤医院行乳腺癌根治术切除的211例有完整病理及生存资料的乳腺癌患者。采用组织芯片技术和免疫组化染色方法,检测p-mTOR在75例Luminal A型乳腺癌患者和136例Luminal B型乳腺癌患者中的表达情况及其与临床病理特征和预后的关系。结果在Luminal A亚型乳腺癌中,p-mTOR表达阳性患者总共38例(50.7%),其中p-mTOR胞浆着色结果与临床分期差异有统计学意义(P=0.04);p-mTOR细胞核或核周着色结果与年龄差异有统计学意义(P=0.03)。Kaplan-Meier生存分析显示p-mTOR总体阳性表达患者的无病生存时间更长,差异有统计学意义(P=0.01)。在Luminal B亚型中p-mTOR阳性表达患者共89例(65.4%)。细胞核或核周着色结果与肿瘤直径和临床分期间差异均有统计学意义(均P<0.05),Kaplan-Meier生存分析显示核或核周着色阳性患者的无病生存时间低于阴性表达者,差异有统计学意义(P<0.01),经Cox多因素分析进一步证实核或核周着色结果是乳腺癌复发转移的独立预后因素(P=0.01,HR=0.182,95%CI 0.060~0.550)。结论 p-mTOR在乳腺癌不同亚型患者中的多样化表达特点提示不同的疾病行为及预后意义。p-mTOR作为Luminal B型乳腺癌的独立预后因素,是潜在的有效靶点。
Objective To investigate the expression of p-mTOR in Luminal A and Luminal B and to analyze the relationship between the expression of p-mTOR and clinicopathological characteristics and its prognosis. Methods A total of 211 breast cancer patients with complete pathology and survival data underwent radical mastectomy at Cancer Hospital of Chinese Academy of Medical Sciences from January 1999 to December 2008 in Peking Union Medical College were selected. The expression of p-mTOR in 75 patients with Luminal A breast cancer and 136 patients with Luminal B breast cancer was detected by tissue microarray technique and immunohistochemistry. The relationship between p-mTOR and clinicopathological features and prognosis was examined. Results A total of 38 patients (50.7%) were positive for p-mTOR expression in Luminal A subtype breast cancer. There was significant difference in the staining results between p-mTOR and clinical stage (P = 0.04) Or perinuclear staining results and age differences were statistically significant (P = 0.03). Kaplan-Meier survival analysis showed that patients with p-mTOR overall positive disease-free survival longer, the difference was statistically significant (P = 0.01). There were 89 patients (65.4%) with positive p-mTOR expression in Luminal B subtype. The results of Kaplan-Meier survival analysis showed that the time to disease-free survival of patients with positive nuclear or perinuclear staining was lower than those with negative expression (P <0.05) The difference was statistically significant (P <0.01). Cox multivariate analysis further confirmed that the nuclear or perinuclear staining was an independent prognostic factor for recurrence and metastasis of breast cancer (P = 0.01, HR = 0.182, 95% CI 0.060-0.550). Conclusion The diverse expression of p-mTOR in patients with different subtypes of breast cancer suggest different disease behaviors and prognostic significance. p-mTOR as an independent prognostic factor for Luminal B breast cancer is a potentially effective target.