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CtIP/RBBP8 表达在乳腺癌中的预后价值。

Prognostic value of CtIP/RBBP8 expression in breast cancer.

机构信息

Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Av. Americo Vespucio s/n, Sevilla, 41092, Spain.

出版信息

Cancer Med. 2013 Dec;2(6):774-83. doi: 10.1002/cam4.141. Epub 2013 Oct 3.

Abstract

CtIP/RBBP8 is a multifunctional protein involved in transcription, DNA replication, DNA repair by homologous recombination and the G1 and G2 checkpoints. Its multiple roles are controlled by its interaction with several specific factors, including the tumor suppressor proteins BRCA1 and retinoblastoma. Both its functions and interactors point to a putative oncogenic potential of CtIP/RBBP8 loss. However, CtIP/RBBP8 relevance in breast tumor appearance, development, and prognosis has yet to be established. We performed a retrospective analysis of CtIP/RBBP8 and RB1 levels by immunohistochemistry using 384 paraffin-embedded breast cancer biopsies obtained during tumor removal surgery. We have observed that low or no expression of CtIP/RBBP8 correlates with high-grade breast cancer and with nodal metastasis. Reduction on CtIP/RBBP8 is most common in hormone receptor (HR)-negative, HER2-positive, and basal-like tumors. We observed lower levels of RB1 on those tumors with reduced CtIP/RBBP8 levels. On luminal tumors, decreased but not absence of CtIP/RBBP8 levels correlate with increased disease-free survival when treated with a combination of hormone, radio, and chemo therapies.

摘要

CtIP/RBBP8 是一种多功能蛋白,参与转录、DNA 复制、同源重组修复以及 G1 和 G2 检验点。其多种功能受其与几种特定因子相互作用的控制,包括肿瘤抑制蛋白 BRCA1 和视网膜母细胞瘤。CtIP/RBBP8 的功能及其相互作用都指向 CtIP/RBBP8 缺失的潜在致癌潜能。然而,CtIP/RBBP8 在乳腺癌的发生、发展和预后中的相关性尚未得到证实。我们通过免疫组织化学法,使用 384 例肿瘤切除手术中获得的石蜡包埋乳腺癌活检组织,对 CtIP/RBBP8 和 RB1 的水平进行了回顾性分析。我们观察到 CtIP/RBBP8 的低表达或无表达与高级别乳腺癌和淋巴结转移相关。CtIP/RBBP8 减少在激素受体(HR)阴性、HER2 阳性和基底样肿瘤中最为常见。我们观察到,在那些 CtIP/RBBP8 水平降低的肿瘤中,RB1 水平也较低。在 luminal 肿瘤中,当接受激素、放疗和化疗联合治疗时,CtIP/RBBP8 水平降低但未缺失与无病生存率增加相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f24/3892382/06d4a2ea3658/cam40002-0774-f1.jpg

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