α-SMA与ALDH1在乳腺癌中的表达及临床意义

摘要/Abstract

摘要： 目的肿瘤-间质相互作用以及肿瘤干细胞与肿瘤的发生发展密切相关。平滑肌肌动蛋白α（α-SMA）和乙醛脱氢酶1（ALDH1）分别为乳腺癌间质成纤维细胞及乳腺癌干细胞的特征性标志物。本研究通过检测α-SMA、ALDH1在乳腺癌中的表达，探讨其与乳腺癌临床预后的关系。方法以免疫组化检测182例乳腺癌患者及36例正常乳腺或良性疾病患者α-SMA、ALDH1的表达，分析二者之间的相关性及其与乳腺癌临床疾病特征及生存预后的关系。结果 α-SMA在正常乳腺组织及乳腺良性病变组织的间质成纤维细胞中无表达（0%），182例乳腺癌中有117例（67.6%）α-SMA阳性；ALDH1在36例正常或良性乳腺疾病和182例乳腺癌中的阳性率分别为16.7%（6/36）和37.9%（69/182）。α-SMA与ALDH1的表达呈正相关（P＜0.05）。α-SMA的表达与肿瘤大小相关（P＜0.05），肿瘤直径大于2cm者α-SMA的阳性率较高；ALDH1的表达与组织分化程度、脉管浸润与否及远处转移与否相关（P＜0.05），分化程度差、有脉管癌栓及远处转移的患者ALDH1阳性率较高。182例乳腺癌患者中α-SMA阳性表达组5年生存率较阴性组无明显降低（P＞0.05）；ALDH1阳性表达组5年生存率较阴性组低，与预后呈负相关（P＜0.05）。α-SMA 和ALDH1的表达情况以及孕激素受体情况、是否接受术前化疗、有无复发、远处转移等6个因素与总生存期有关（P＜0.05），均为乳腺癌的独立预后因素。结论 α-SMA、ALDH1均可能与乳腺癌的发生及发展有关。二者之间的表达正相关，提示肿瘤相关成纤维细胞（TAFs）可能与乳腺癌的干性有关。联合检测α-SMA、和ALDH1有助于判断疾病的恶性程度、浸润能力及转移潜能，可作为预测乳腺癌预后的新指标。

关键词: 乳腺癌, α-SMA, ALDH1, 预后因素乳腺癌, α-SMA, ALDH1, 预后因素

中图分类号:

R737.9

陈珊珊姚和瑞. α-SMA与ALDH1在乳腺癌中的表达及临床意义[J]. 岭南现代临床外科, 2012, 12(02): 81-86.

参考文献

[1]Shackleton M, Vaillant F, Simpson KJ, et al.Generation of a functional mammary gland from a single stenl cell[J].Nature,2006,439(7072):84-88
[2]许良中, 杨文涛.免疫组织化学反应结果的判断标准[J].中国癌症杂志,1996,6:229-231
[3]Ginestier C, Hur MH, Charafe-Jauffret E, et al.ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome[J].Cell stem cell,2007,1(5):556-557
[4]Li C, Heidt DG, Dalerba P, et al.Identification of pancreatic cancer stem cells[J].Cancer Res,2007,67(3):1030-1037
[5]Chen YC, Chen YW, Hsu HS, et al.Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer[J].Biochem Biophys Res Commun,2009,385(3):307-313
[6]Jiang F, Qiu Q, Khanna A, et al.Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer[J].Mol Cancer Res,2009,7(3):330-338
[7]Kim H, Lapointe J, Kaygusuz G, et al.The retinoic acid synthesis gene ALDH1a2 is a candidate tumor suppressor in prostate cancer[J].Cancer Res,2005,65(18):8118-8124
[8]Seigel GM, Campbell LM, Narayan M, et al.Cancer stem cell characteristics in retinoblastoma[J].Molecular vision,2005,11:729-737
[9]Huang EH, Hynes MJ, Zhang T, et al.Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis[J].Cancer Res,2009,69(8):3382-3389
[10]Zeisberg EM, Potenta S, Xie L, et al.Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts[J].Cancer Res,2007,67(21):10123-10128
[11]Chauhan H, Abraham A, Phillips JRA, et al.There is more than one kind of myofibroblast: analysis of CD34 expression in benign, in situ, and invasive breast lesions[J].J Clin Pathol,2003,56(4):271-276
[12]Dewan MZ, Ahmed S, Iwasaki Y, et al.Stromal cell-derived factor-1 and CXCR4 receptor interaction in tumor growth and metastasis of breast cancer[J].Biomed Pharmacother,2006,60(6):273-276
[13]Orimo A, Gupta PB, Sgroi DC, et al.Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion[J].Cell,2005,121(3):335-348
[14]Giannoni E, Bianchini F, Calorini L, et al.Cancer associated fibroblasts exploit reactive oxygen species through a proinflammatory signature leading to epithelial mesenchymal transition and stemness[J].Antioxid Redox Signal,2011,14(12):2361-2371
[15]Huang M, Li Y, Zhang H, et al.Breast cancer stromal fibroblasts promote the generation of CD44+CD24- cells through SDF-1/CXCR4 interaction[J].J Exp Clin Cancer Res,2010,29:80-