The prognostic significance of PELP1 expression in invasive breast cancer with emphasis on the ER-positive luminal-like subtype
The prognostic significance of PELP1 expression in invasive breast cancer with emphasis on the ER-positive luminal-like subtype
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DOI：
10.1007/s10549-009-0419-9
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发表时间：
2010-04-01
影响因子：
3.8
通讯作者：
Ellis, Ian O.
中科院分区：
文献类型：
--
作者：
Habashy, Hany Onsy;Powe, Desmond G.;Ellis, Ian O.
雌激素受体（ER）的转录功能受几种辅调节因子如PELP 1（脯氨酸、谷氨酸和亮氨酸富集蛋白1）的影响。本研究使用组织微阵列和免疫组织化学，旨在探索PELP 1蛋白表达在大量连续浸润性乳腺癌患者（1，162例患者）中的临床和生物学相关性，特别强调其在ER阳性/管腔样肿瘤中的作用。我们的研究结果表明，PELP 1表达增加与肿瘤体积较大、组织学分级较高、有丝分裂计数较高以及基底细胞角蛋白（CK）（CK 14; P = 0.018和CK 5/6; P = 0.029）、P-钙粘蛋白（P = 0.002）、p53和MIB 1（P = 0.018）阳性表达相关。PELP 1表达与ER（P = 0.002）、孕酮（PgR）（P = 0.004）、雄激素（AR）受体（P < 0.001）和管腔CK（CK 18; P = 0.027）表达呈负相关。PELP 1表达与较短乳腺癌特异性生存期（BCSS）之间的显著相关性（P = 0.002）和无病生存期（DFI）多因素考克斯风险分析显示PELP 1表达是BCSS缩短的独立预测因子（风险比（HR）= 1.349，P = 0.006）和更短的DFI（HR = 1.255，P = 0.011）。在ER阳性/管腔样组（n = 768）中，PELP 1表达与其他临床病理变量显示出相似的相关性，并且是较短DFI的独立预测因子（HR = 1.256，P = 0.036）。总之，PELP 1蛋白表达是乳腺癌中BCSS和DFI较短的独立预后预测因子，其表达升高与预后不良的标志物呈正相关。PELP 1似乎在评估ER阳性乳腺癌患者的临床结局方面具有潜在的应用价值。
The transcription functions of oestrogen receptors (ER) are influenced by several coregulators such as PELP1 (proline, glutamate and leucine rich protein 1). The aim of the present study, which uses tissue microarrays and immunohistochemistry, is to explore the clinical and biological relevance of PELP1 protein expression in a large series of consecutive patients (1,162 patients) with invasive breast cancers with particular emphasis on its role in the ER-positive/luminal-like class of tumours. Our results showed that increased PELP1 expression is associated with tumours of larger size, higher histological grade, higher mitotic count, and with positive expression of basal cytokeratins (CK) (CK14; P = 0.018 and CK5/6; P = 0.029), P-cadherin (P = 0.002), p53 and MIB1 (P = 0.018). There was an inverse association between PELP1 expression and ER (P = 0.002), progesterone (PgR) (P = 0.004), androgen (AR) receptor (P < 0.001), and luminal CK (CK18; P = 0.027) expression. A significant association between PELP1 expression and shorter breast cancer specific survival (BCSS) (P = 0.002) and disease-free survival (DFI) (P = 0.006) was found. Multivariate Cox hazard analysis showed that PELP1 expression was an independent predictor of shorter BCSS (Hazard ratio (HR) = 1.349, P = 0.006) and shorter DFI (HR = 1.255, P = 0.011). In the ER-positive/luminal-like group (n = 768), PELP1 expression showed similar association with other clinicopathological variables and was an independent predictor of shorter DFI (HR = 1.256, P = 0.036). In conclusion, PELP1 protein expression is an independent prognostic predictor of shorter BCSS and DFI in breast cancer and its elevated expression is positively associated with markers of poor outcome. PELP1 appears to have a potential application in assessing the clinical outcome of patients with ER-positive breast cancer.