Oesterreich S, Hilsenbeck S G, Ciocca D R, Allred D C, Clark G M, Chamness G C, Osborne C K, Fuqua S A
Department of Medicine, Division of Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7884, USA.
Clin Cancer Res. 1996 Jul;2(7):1199-206.
Heat shock protein 27 (hsp27) belongs to the family of heat shock proteins and is thought to be involved in thermotolerance, cell proliferation, drug resistance, and chaperone processes. The aim of this study was to investigate whether hsp27 levels are correlated with clinical outcome in axillary lymph node-negative breast cancer patients. We describe a Western blot study measuring hsp27 levels in 425 patients and an immunohistochemistry (IHC) study analyzing 788 patients. Results obtained by both methods were concordant. Univariate survival analysis was performed considering hsp27 either as an optimally dichotomized variable or as a continuous variable. Additional data include age at biopsy, tumor size, estrogen receptor (ER) and progesterone receptor status, tumor ploidy and percentage of cells in S phase, and adjuvant therapy. hsp27 levels correlated positively with ER status (P = 0.0001 in Western blot and IHC study), progesterone receptor status (P = 0.0001 in Western blot and IHC study), and aneuploidy (Western blot study, P = 0.0012; IHC study, P = 0.0004) but not with tumor size (Western blot study, P = 0.69; IHC, P = 0.53) or S phase (Western blot study, P = 0.19; IHC study, P = 0.38). Overall, there was no relationship between hsp27 expression and disease-free survival (Western blot study, P = 0.70/0.54; IHC, P = 0.47/0.30) or overall survival (Western blot study, P = 0.16/0.15; IHC, P = 0.46/0.78). Exploratory subset analyses defined by ER status and use of adjuvant treatment indicated that in ER+/untreated patients, high hsp27 levels correlated modestly with shorter disease-free survival (Western blot, P = 0.04/0.04; IHC, P = 0.11/0. 03). hsp27 is not a useful prognostic marker for the clinic in axillary lymph node-negative patients. However, the finding of modest prognostic value of hsp27 in the subgroup of ER+/untreated patients raises new questions about the biological function of hsp27 in breast cancer.
热休克蛋白27（hsp27）属于热休克蛋白家族，被认为与耐热性、细胞增殖、耐药性及伴侣蛋白过程有关。本研究旨在调查hsp27水平是否与腋窝淋巴结阴性乳腺癌患者的临床结局相关。我们描述了一项对425例患者进行hsp27水平检测的蛋白质印迹研究以及一项对788例患者进行分析的免疫组织化学（IHC）研究。两种方法得到的结果一致。单因素生存分析将hsp27作为最佳二分变量或连续变量进行考量。其他数据包括活检时的年龄、肿瘤大小、雌激素受体（ER）和孕激素受体状态、肿瘤倍体及S期细胞百分比，以及辅助治疗情况。hsp27水平与ER状态呈正相关（蛋白质印迹和IHC研究中P = 0.0001）、与孕激素受体状态呈正相关（蛋白质印迹和IHC研究中P = 0.0001）以及与非整倍体呈正相关（蛋白质印迹研究中P = 0.0012；IHC研究中P = 0.0004），但与肿瘤大小无关（蛋白质印迹研究中P = 0.69；IHC研究中P = 0.53）或与S期无关（蛋白质印迹研究中P = 0.19；IHC研究中P = 0.38）。总体而言，hsp27表达与无病生存期（蛋白质印迹研究中P = 0.70/0.54；IHC研究中P = 0.47/0.30）或总生存期（蛋白质印迹研究中P = 0.16/0.15；IHC研究中P = 0.46/0.78）均无关联。根据ER状态和辅助治疗使用情况进行的探索性亚组分析表明，在ER阳性/未接受治疗的患者中，hsp27高水平与较短的无病生存期呈适度相关（蛋白质印迹研究中P = 0.04/0.04；IHC研究中P = 0.11/0.03）。对于腋窝淋巴结阴性患者，hsp27并非临床有用的预后标志物。然而，hsp27在ER阳性/未接受治疗患者亚组中具有适度预后价值这一发现，引发了关于hsp27在乳腺癌中生物学功能的新问题。
