Baldacchino Shawn, Wastall Laura M, Saliba Christian, Hughes Thomas A, Scerri Christian, Berwick Angelene, Speirs Valerie, Hanby Andrew M, Grech Godfrey
1 Laboratory of Molecular Pathology, Department of Pathology, Faculty of Medicine & Surgery, University of Malta, Msida, Malta.
2 School of Medicine, University of Leeds, Leeds, UK.
Tumour Biol. 2017 Oct;39(10):1010428317722064. doi: 10.1177/1010428317722064.
CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours and generally correlated with higher tumour grade and therapeutic resistance. CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A, stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although further biological mechanisms for CIP2A are yet to be defined. CIP2A protein expression was studied by immunohistochemistry in oestrogen receptor-positive primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total, 51 cases presented with a relapse or metastasis during adjuvant treatment with tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored separately for cytoplasmic, nuclear, or membranous staining, and scores were tested for statistically significant relationships with clinicopathological features. Membranous CIP2A was preferentially expressed in cases who experienced a recurrence during tamoxifen treatment thus predicting a worse overall survival (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p < 0.001). Cox multivariate analysis indicates that it is an independent prognostic indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the assessment of membranous CIP2A expression as a potential novel prognostic and predictive indicator for tamoxifen resistance and recurrence within oestrogen receptor-positive breast cancer.
CIP2A正逐渐成为一种癌蛋白，在许多肿瘤中普遍过表达，通常与更高的肿瘤分级和治疗抗性相关。CIP2A通过抑制蛋白磷酸酶2A、稳定MYC以及促进上皮-间质转化来驱动致癌潜能，不过CIP2A的进一步生物学机制尚待明确。采用免疫组织化学方法对从利兹组织库获取的雌激素受体阳性原发性乳腺癌（n = 250）中的CIP2A蛋白表达进行了研究。总共有51例患者在他莫昔芬辅助治疗期间出现复发或转移，被视为他莫昔芬耐药。分别对细胞质、细胞核或细胞膜染色的CIP2A表达进行评分，并测试评分与临床病理特征之间的统计学显著关系。细胞膜CIP2A在他莫昔芬治疗期间出现复发的病例中优先表达，因此预示着总体生存期更差（对数秩 = 8.357，p = 0.004）和无病生存期更差（对数秩 = 21.766，p < 0.001）。Cox多变量分析表明，它是总体生存期（风险比 = 4.310，p = 0.013）和无病生存期（风险比 = 5.449，p = 0.002）的独立预后指标。在本研究中，我们提议将细胞膜CIP2A表达评估作为雌激素受体阳性乳腺癌中他莫昔芬耐药和复发的一种潜在新型预后和预测指标。
