HEAT-SHOCK PROTEIN-HSP70 IN PATIENTS WITH AXILLARY LYMPH NODE-NEGATIVE BREAST-CANCER - PROGNOSTIC IMPLICATIONS
HEAT-SHOCK PROTEIN-HSP70 IN PATIENTS WITH AXILLARY LYMPH NODE-NEGATIVE BREAST-CANCER - PROGNOSTIC IMPLICATIONS
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DOI：
10.1093/jnci/85.7.570
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发表时间：
1993-04-07
期刊：
影响因子：
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通讯作者：
MCGUIRE, WL
中科院分区：
文献类型：
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作者：
CIOCCA, DR;CLARK, GM;MCGUIRE, WL
背景：热休克（应激反应）蛋白的细胞合成在各种环境和病理生理应激条件下增加。70-kd热休克蛋白（hsp70）被认为参与蛋白-蛋白相互作用，包括人类c-myc癌基因和p53（也称为TP53）肿瘤抑制基因的蛋白产物。目的：本研究的目的是探讨hsp70表达升高是否可能是乳腺癌所经历的生物应激的一个指标，从而可能预测疾病结局。方法：采用Western blot法检测腋窝淋巴结阴性患者原发乳腺肿瘤组织中hsp70的表达水平。我们对162例原发性乳腺癌进行了探索性数据分析，并构建了hsp70表达水平的预后指标。hsp70表达的最佳切点被认为是产生两组患者无病生存最大分离的值。然后通过单变量和多变量分析在345例肿瘤中验证了该切点。数据分析包括总生存期、无病生存期、肿瘤大小、患者年龄、雌激素受体和孕激素受体状态、倍性（DNA含量）以及流式细胞术测定的S期细胞百分比。结果：在单因素和多因素分析中，hsp70的表达都是一个有用的预后因素。肿瘤高表达hsp70的患者无病生存期明显缩短（P = 0.006）。其他具有统计学意义的因素为s期分数（P = 0.008）和肿瘤大小（P = 0.01）。对于接受辅助治疗的患者，hsp70是疾病复发的唯一独立预测因子（P = 0.05）。对于直径为1-3 cm的肿瘤，hsp70 （P = 0.008）和s期分数（P = 0.02）是具有统计学意义的复发预测因子。结论：检测淋巴结阴性乳腺癌原发肿瘤中hsp70的表达可能有助于识别疾病复发的高风险患者，从而影响手术后治疗的决策。意义：未来的研究应确定免疫组织化学检测hsp70是否可用于预测临床结果，并更好地了解hsp70与各种治疗方式效果之间的关系。
Background: Cell synthesis of heat shock (stress-response) proteins is increased by a variety of environmental and pathophysiological stressful conditions. The 70-kd heat shock protein (hsp70) is thought to be involved in protein-protein interactions including those of the protein products of the human c-myc oncogene and the p53 (also known as TP53) tumor suppressor gene. Purpose: The purpose of this study was to investigate whether elevated hsp70 expression may be an indicator of biological stress experienced by a breast cancer and may, therefore, predict disease outcome. Methods: levels of hsp70 were determined by Western blot analysis in primary breast tumors from patients with negative axillary lymph nodes. We performed exploratory data analyses on a set of 162 primary breast cancers and constructed prognostic indexes of hsp70 expression levels. The optimal cutpoint for hsp70 expression was considered to be the value yielding the greatest separation for disease-free survival for the resulting two groups of patients. That cutpoint was then validated in a set of 345 tumors by univariate and multivariate analyses. Data were analyzed for overall survival, disease-free survival, tumor size, and patient age, as well as estrogen receptor and progesterone receptor status, ploidy (DNA content), and percentage of cells in S phase as determined by flow cytometry. Results: Expression of hsp70 emerged as a useful prognostic factor, both in univariate and in multivariate analyses. Patients whose tumors had high expression of hsp70 had significantly shorter disease-free survival (P = .006). The other statistically significant factors were S-phase fraction (P = .008) and tumor size (P = .01). For patients who received adjuvant therapy, hsp70 was the only independent predictor of disease recurrence (P = .05). For those with tumors 1-3 cm in diameter, hsp70 (P = .008) and S-phase fraction (P = .02) were statistically significant predictors of recurrence. Conclusions: Measurement of hsp70 expression in primary tumors from patients with node-negative breast cancer may be useful in identifying patients at high risk for disease recurrence and thus may affect decisions regarding treatment after surgery. Implications: Future studies should be performed to determine if detection of hsp70 by immunohistochemistry can be used to predict clinical outcome and to better understand the relationships between hsp70 and the effects of various treatment modalities.