PICK-1蛋白在多种肿瘤中的表达及在乳腺癌的临床意义

The Expression of PICK-1 Protein in Breast Cancer and Its Significance

目的:主要探讨乳腺浸润性癌组织中PICK-1蛋白的表达与该肿瘤临床病理、其他生物学指标以及患者预后的相关性。方法:采用组织芯片免疫组织化学染色方法检测496例乳腺浸润性癌组织中PICK-1、ER、PR、HER2/neu、TlMP-1等蛋白的表达情况及表达间的相关性,以及PICK-1蛋白在不同分子亚型乳腺癌中的表达情况及对预后的影响。结果:PICK-1蛋白在乳腺癌组织中的表达率为27.22%,肿瘤细胞中PICK-1的高表达与淋巴结受累和高组织学分级相关(P均<0.001),且与HER2/neu表达相关(P<0.001),而与雌孕激素受体状态无关(P>0.05),同时该蛋白的表达与TIMP-1表达呈正相关(P=0.002)。PICK-1蛋白表达与患者总生存期缩短相关,分层分析显示PICK-1仅对淋巴结阳性患者的预后有影响,同时对HER2/neu不同状态患者的影响不同,其中对三阴性乳腺癌(HR-HER-)预后影响最大。单因素分析显示乳腺肿瘤直径、组织学分级、淋巴结状态、HR状态、HER2/neu表达、TIMP-1表达、肿瘤细胞表达PICK-1均是有意义的预后指标;但多因素分析显示仅肿瘤直径、组织学分级、淋巴结状态、HER2/neu袁达和PICK-1表达是独立的预后因素。结论:PICK-1蛋白与浸润性乳腺癌的侵袭和转移特性相关,同时有可能作为患者预后不良的指标,尤其是对于三阴性乳腺癌的预后意义更为显著。

Objective： To investigate the expression of PICK-1 protein in invasive breast carcinoma and to determine its relationship with the clinicopathologic features, other biological indicators, and prognosis. Methods： We used immunohistochemistry to detect the expressions of PICK-1, estrogen receptor, progesterone receptor, HER2/neu, and TIMP-1 in paraffin-embedded tissue microarrays from 496 cases of invasive breast carcinoma. Results： PICK-1 protein was detected in the cytoplasm of malignant cells in 27.22% cases. High expression of PICK-1 protein within cancer cells was associated with lymph node infiltration and higher grade （P〈0.001） and was positively correlated with HER2/neu expression （P〈0.001）. High expression of PICK-1 protein was also associated with expression of TIMP-1 （P=0.002）. Moreover, high expression of PICK-1 was associated with short overall survival and subsets of positive lymph node. Tumor-derived PICK-1 has different impact on patients with different HER2/neu status, especially for HR-HER-type. Univariate survival analysis showed that tumor size, grade, lymph node status, HR status, HER2/neu expression, TIMP-1 expression, and PICK-1 expression were prognostic factors. Multivariate survival analysis showed that tumor size, grade, lymph node status, HER2/neu expression, and PICK-1 expression were independent prognostic factors. Conclusion： PICK-1 protein is correlated with an invasive and metastatic tumor phenotype and may be used as a prognostic marker of breast carcinoma.