The prognostic value of apoptotic and proliferative markers in breast cancer
The prognostic value of apoptotic and proliferative markers in breast cancer
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DOI：
10.1007/s10549-013-2748-y
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发表时间：
2013-11-01
影响因子：
3.8
通讯作者：
Kuppen, Peter J. K.
中科院分区：
文献类型：
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作者：
Engels, Charla C.;Ruberta, Francesca;Kuppen, Peter J. K.
早期乳腺癌（BC）诊断能力的提高导致更多的早期发现，更好的生存率和低复发率是几十年来取得的里程碑之一。上述对临床医生提出了关于最佳治疗的挑战，其中应避免过度和治疗不足。经典的预后和预测因素不足以在该患者组中进行个性化的辅助治疗选择。更好地表征肿瘤的关键可能在于个体肿瘤的生物学基础。我们假设与细胞增殖和凋亡相关的标志物以及这两个过程在肿瘤发展中的平衡将预测临床结果。我们的研究人群（N = 822）包括1985年至1996年间在我们中心主要接受手术治疗的所有早期BC患者。可用肿瘤组织切片（87%,714/822）进行免疫组织化学染色，检测p53、active-caspase-3和Ki67的表达。在该队列中，分别有43%（304/714）和18%（126/714）的患者进行了生化C2P（a (R)）风险预测和caspase-3检测。分析上述标记物单独或联合的表达数据。结果表明，无论是单一的还是联合的标记物，无论是凋亡源还是增殖源，都与临床预后有关。当结合p53、活性caspase-3和Ki67状态的数据时，可以看到危险比的加性效应。在I级乳腺肿瘤的多变量分析中，集合预后凋亡-增殖亚型与总生存期（p = 0.024）和无复发期（p = 0.001）均有显著相关性。肿瘤细胞凋亡和增殖的联合标志物代表肿瘤的侵袭性。我们在本研究中提出的凋亡-增殖亚型代表了具有坚实生物学基础的临床预后特征，并为准确识别需要积极治疗方法的I级BC患者提供了一种有希望的方法，从而促进了BC疾病的精准医学。
Increasing ability of early breast cancer (BC) diagnosis leading to more early stage detection, better survival, and low relapse marks one of the milestones achieved over the decades. Foregoing poses a challenge for clinicians regarding optimal treatment, in which over- and under-treatment should be avoided. Classical prognostic and predictive factors fall short for individualized adjuvant therapy selection in this patient group. The key to better characterization may be found in the biology underlying individual tumors. We hypothesized that markers related to cellular proliferation and apoptosis and the balance between these two processes in tumor development will be predictive for clinical outcome. Our study population (N = 822) consisted of all early stage BC patients primarily treated with surgery in our center between 1985 and 1996. Sections of available tumor tissue (87 %, 714/822) were immunohistochemically stained for expression of p53, active-caspase-3, and Ki67. In 43 % (304/714) and 18 % (126/714) of this cohort, respectively, a biochemical C2P(A (R)) risk prediction and caspase-3 assay were performed. Expression data of the mentioned markers, single, or combined, were analyzed. Results showed that both the single and combined markers, whether of apoptotic or proliferative origin had associations with clinical outcome. An additive effect was seen for the hazard ratios when data on p53, active caspase-3, and Ki67 status were combined. The assembled prognostic apoptotic-proliferative subtype showed significant association for both the overall survival (p = 0.024) and relapse-free period (p = 0.001) in the multivariate analyses of grade I breast tumors. Combined markers of tumor cell apoptosis and proliferation represent tumor aggressiveness. The apoptotic-proliferative subtypes that we present in this study represent a clinical prognostic profile with solid underlying biological rationale and pose a promising method for accurate identification of grade I BC patients in need of an aggressive therapeutic approach, thus contributing to precision medicine in BC disease.