Søiland Håvard, Janssen Emiel A M, Kørner Hartwig, Varhaug Jan Erik, Skaland Ivar, Gudlaugsson Einar, Baak Jan P A, Søreide Jon Arne
Department of Surgery, Stavanger University Hospital, Stavanger, Norway.
Breast Cancer Res Treat. 2009 Feb;113(3):519-28. doi: 10.1007/s10549-008-9955-y. Epub 2008 Mar 11.
Apolipoprotein D (ApoD) is a lipocalin involved in various cellular processes, including cytoprotection. We retrospectively evaluated its prognostic impact in 272 women (median age 63 (range 21-89) years, with operable breast cancer (Stage I or IIa) treated according to national guidelines, stratified by age and menopausal status, with a median long-term follow-up of 12 years. ApoD, estrogen receptor-alpha (ERalpha), and progesterone receptor (PR) positivity were determined by quantitative immunohistochemistry in tissue microarrays taken from the invasive front of the tumors and in whole tumor sections. ApoD was expressed in 50% of the tumors. Diffuse nuclear and cytoplasmic (ApoD(CN)), but not granular cytoplasmic ApoD expression in the invasive front was a detrimental factor for elderly patients over 70 years of age, (n = 83), but not for younger and pre-menopausal patients. ApoD(CN )expression correlated with lymph node metastases (P = 0.04). Moreover, a correlation between ApoD(CN )localization and age over 70 years was observed (P = 0.03). In the elderly, ApoD(CN) positive tumors had both a significantly shorter relapse-free survival (all locations) (P = 0.02) and a decreased breast cancer-specific survival (P < 0.0001). Moreover, the prognostic importance of ApoD was dose dependent (P = 0.002) Multivariate analysis confirmed the prognostic value of ApoD(CN). When the elderly patients were stratified by nodal status, ApoD showed prognostic importance only in the node positive patients (n = 30) (HR = 9.6; 95% CI = 2.3-40.4). The potential relevance of ApoD in this increasingly frequent group of breast cancer patients should be further explored.
载脂蛋白D（ApoD）是一种参与多种细胞过程（包括细胞保护）的脂质运载蛋白。我们回顾性评估了其对272例女性（中位年龄63岁（范围21 - 89岁））的预后影响，这些女性患有可手术乳腺癌（I期或IIa期），按照国家指南进行治疗，根据年龄和绝经状态分层，中位长期随访时间为12年。通过定量免疫组织化学在取自肿瘤浸润前沿的组织微阵列和整个肿瘤切片中测定ApoD、雌激素受体α（ERα）和孕激素受体（PR）的阳性情况。50%的肿瘤表达ApoD。在浸润前沿弥漫性核和细胞质（ApoD(CN)）表达，但不是颗粒状细胞质ApoD表达，对70岁以上老年患者（n = 83）是一个不利因素，而对年轻和绝经前患者不是。ApoD(CN)表达与淋巴结转移相关（P = 0.04）。此外，观察到ApoD(CN)定位与70岁以上年龄之间存在相关性（P = 0.03）。在老年人中，ApoD(CN)阳性肿瘤的无复发生存期（所有部位）显著缩短（P = 0.02），且乳腺癌特异性生存率降低（P < 0.0001）。此外，ApoD的预后重要性呈剂量依赖性（P = 0.002）。多变量分析证实了ApoD(CN)的预后价值。当老年患者按淋巴结状态分层时，ApoD仅在淋巴结阳性患者（n = 30）中显示出预后重要性（HR = 9.6；95% CI = 2.3 - 40.4）。ApoD在这一越来越常见的乳腺癌患者群体中的潜在相关性应进一步探索。
