Eppenberger-Castori Serenella, Moore Dan H, Thor Ann D, Edgerton Susan M, Kueng Willy, Eppenberger Urs, Benz Christopher C
Stiftung Tumorbank Basel and Department of Research, University Clinics, Basel, Switzerland.
Int J Biochem Cell Biol. 2002 Nov;34(11):1318-30. doi: 10.1016/s1357-2725(02)00052-3.
To explore the hypothesis that aging not only increases breast cancer incidence but also alters breast cancer biology, we correlated patient age and diagnosis with tumor histology, stage and biomarkers independently determined from two different tumor archives: an American collection of approximately 800 paraffin-embedded and immunohistochemically analyzed primary breast cancers, and an European collection of approximately 3000 cryobanked primary breast cancers analyzed by ligand-binding and enzyme immunoassay (EIA). The prognostic biomarkers chosen for comparison represented surrogate measures of tumor: (i). proliferation, growth and genetic instability (mitotic and apoptotic indices, Ki-67/MIB-1-positivity, nuclear grade, p53-positivity), (ii). endocrine-dependence (estrogen receptor (ER), progesterone receptors (PR), pS2, Bcl2), (iii). growth factor receptor-dependence (ErbB2, EGFR/ErbB1), and (iv). angiogenic, invasive and proteolytic potential (uPA, PAI-1, Cathepsin D, VEGF). No biomarker reflecting tumor angiogenic, invasive or proteolytic potential showed a significant correlation with patient age at diagnosis. In contrast, significant inverse correlations (|r|>0.1; P< or =0.05) were observed for all measures of tumor growth and genetic instability as well as growth factor receptor overexpression (ErbB2 or EGFR positivity). Only one marker of endocrine-dependence, ER expression, showed a significant positive correlation with patient age at diagnosis. In summary, these findings support the hypothesis that breast cancer biology is significantly affected by patient age. In particular, breast tumors arising in older patients have slower growth rates, are more likely to be ER-positive, and are less likely to be p53-positive, EGFR-positive or ErbB2-positive.
为了探究衰老不仅会增加乳腺癌发病率，还会改变乳腺癌生物学特性这一假说，我们将患者年龄及诊断结果与肿瘤组织学、分期和生物标志物进行了关联分析，这些生物标志物是从两个不同的肿瘤库独立测定得出的：一个是美国收集的约800例经石蜡包埋并进行免疫组化分析的原发性乳腺癌；另一个是欧洲收集的约3000例通过配体结合和酶免疫测定（EIA）分析的冷冻保存的原发性乳腺癌。选择用于比较的预后生物标志物代表了肿瘤的替代指标：（i）增殖、生长和基因不稳定性（有丝分裂和凋亡指数、Ki-67/MIB-1阳性、核分级、p53阳性），（ii）内分泌依赖性（雌激素受体（ER）、孕激素受体（PR）、pS2、Bcl2），（iii）生长因子受体依赖性（ErbB2、EGFR/ErbB1），以及（iv）血管生成、侵袭和蛋白水解潜能（uPA、PAI-1、组织蛋白酶D、VEGF）。没有任何反映肿瘤血管生成、侵袭或蛋白水解潜能的生物标志物与诊断时的患者年龄呈现显著相关性。相反，对于所有肿瘤生长和基因不稳定性指标以及生长因子受体过表达（ErbB2或EGFR阳性），均观察到显著的负相关（|r|>0.1；P≤0.05）。仅有一种内分泌依赖性标志物，即ER表达，与诊断时的患者年龄呈现显著正相关。总之，这些发现支持了乳腺癌生物学特性受患者年龄显著影响这一假说。特别是，老年患者发生的乳腺肿瘤生长速度较慢，更有可能为ER阳性，且不太可能为p53阳性、EGFR阳性或ErbB2阳性。
