Chuthapisith Suebwong, Bean Beverley E, Cowley Gerard, Eremin Jennifer M, Samphao Srila, Layfield Robert, Kerr Ian D, Wiseman Janice, El-Sheemy Mohamed, Sreenivasan Thiagarajan, Eremin Oleg
Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Division of Surgery, Queen's Medical Centre, University of Nottingham, E Floor, West Block, Nottingham NG7 2UH, UK.
PathLinks, Lincoln County Hospital, Lincoln, UK.
Eur J Cancer. 2009 May;45(7):1274-1281. doi: 10.1016/j.ejca.2008.12.026. Epub 2009 Jan 24.
Neoadjuvant chemotherapy is used in women who have large or locally advanced breast cancers. However, up to 70% of women who receive neoadjuvant chemotherapy fail to achieve a complete pathological response in their primary tumour (a surrogate marker of long-term survival). Five proteins, previously identified to be linked with chemoresistance in our in vitro experiments, were identified histochemically in pre-treatment core needle biopsies from 40 women with large or locally advanced breast cancers. Immunohistochemical staining with the five proteins showed no single protein to be a predictor of response to chemotherapy. However, pre-treatment breast cancer specimens that were annexin-A2 positive but annexin-A1 negative correlated with a poor pathological response (p=0.04, Fisher's exact test). The mechanisms by which annexins confer chemoresistance have not been identified, but may be due to inhibition of apoptosis. Annexin-A1 has been shown to enhance apoptosis, whilst annexin-A2, by contrast, inhibits apoptosis.
新辅助化疗用于患有大型或局部晚期乳腺癌的女性。然而,接受新辅助化疗的女性中,高达70%的患者原发肿瘤未能达到完全病理缓解(这是长期生存的替代指标)。在我们的体外实验中,先前已确定与化疗耐药相关的五种蛋白质,在40名患有大型或局部晚期乳腺癌的女性的治疗前粗针活检组织中进行了组织化学鉴定。用这五种蛋白质进行免疫组织化学染色显示,没有一种蛋白质可作为化疗反应的预测指标。然而,膜联蛋白A2阳性但膜联蛋白A1阴性的治疗前乳腺癌标本与不良病理反应相关(p=0.04,Fisher精确检验)。膜联蛋白赋予化疗耐药性的机制尚未明确,但可能是由于抑制了细胞凋亡。已证明膜联蛋白A1可增强细胞凋亡,而相比之下,膜联蛋白A2则抑制细胞凋亡。