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目的探讨蛋白磷酸酶2A的癌性抑制因子(CIP2A)在乳腺导管上皮的恶性转化过程中的作用及其预测浸润性导管癌患者预后的能力。方法收集乳腺正常导管上皮(正常对照)、普通型增生(UDH)、不典型增生(ADH)、导管内癌(DCIS)及浸润性导管癌(IDC)的石蜡标本322例,采用免疫组织化学染色法检测其中CIP2A的表达。通过χ~2检验分析各组间CIP2A的表达差异,并验证CIP2A与DCIS及IDC患者临床病理学参数的关系。通过Kaplan-Meier生存分析及Cox比例风险回归模型分析CIP2A与IDC患者预后的关系。结果 CIP2A在正常对照组、UDH组、ADH组、DCIS组及IDC组的表达率分别为6.66%、5.13%、6.66%、32.35%及32.45%。CIP2A分别在UDH组与DCIS组、UDH组与IDC组的表达差异有统计学意义(P=0.004 3、P=0.004 0)。CIP2A表达与DCIS患者的高组织学分级及高Ki67指数呈显著相关性(P均<0.05)。在IDC患者中,CIP2A表达与Cerb B2(Her-2)阳性、高Ki67指数、高TNM分期及淋巴结转移呈显著相关性(P均<0.05)。CIP2A阳性患者5年无病生存率和总生存率显著降低,且CIP2A可以作为一种独立的预后因子预测IDC患者预后。结论 CIP2A在乳腺导管上皮癌变过程中可能发挥重要作用。CIP2A有望用于监测导管上皮癌变,并预测IDC患者的预后。
Objective To investigate the role of protein phosphatase 2A (CIP2A) in malignant transformation of breast ductal epithelium and its prognostic value in invasive ductal carcinoma. Methods 322 paraffin-embedded specimens of normal ductal epithelium (normal control), common hyperplasia (UDH), atypical hyperplasia (ADH), ductal carcinoma (DCIS) and invasive ductal carcinoma (IDC) were collected. Immunohistochemical staining Method to detect CIP2A expression. The differences of CIP2A expression among groups were analyzed by χ ~ 2 test, and the relationship between CIP2A and clinicopathological parameters of DCIS and IDC patients was verified. The relationship between CIP2A and the prognosis of IDC patients was analyzed by Kaplan-Meier survival analysis and Cox proportional hazards regression model. Results The expression rates of CIP2A in normal control group, UDH group, ADH group, DCIS group and IDC group were 6.66%, 5.13%, 6.66%, 32.35% and 32.45%, respectively. The expression of CIP2A in UDH group and DCIS group, UDH group and IDC group were significantly different (P = 0.004 3, P = 0.004 0). There was a significant correlation between CIP2A expression and histological grade and Ki67 index (all P <0.05). In IDC patients, CIP2A expression was significantly correlated with Cerb B2 (Her-2) positive, high Ki67 index, high TNM stage and lymph node metastasis (all P <0.05). CIP2A-positive patients 5-year disease-free survival and overall survival was significantly lower, and CIP2A as an independent prognostic factor in predicting the prognosis of IDC patients. Conclusion CIP2A may play an important role in carcinogenesis of breast ductal epithelium. CIP2A is expected to be used to monitor ductal carcinogenesis and predict the prognosis of IDC patients.