Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520-8040, USA.
Int J Radiat Oncol Biol Phys. 2013 Oct 1;87(2):344-8. doi: 10.1016/j.ijrobp.2013.05.052. Epub 2013 Aug 1.
Ki-67 is a human nuclear protein whose expression is strongly up-regulated in proliferating cells and can be used to determine the growth fraction in clonal cell populations. Although there are some data to suggest that Ki-67 overexpression may be prognostic for endpoints such as survival or postmastectomy recurrence, further elucidation of its prognostic significance is warranted. Specifically after breast conservation therapy (BCT) (defined in this setting as breast-conserving surgery and adjuvant radiation therapy), whether Ki-67 predicts for locoregional recurrence has not been investigated. The purpose of this study was to assess Ki-67 expression in a cohort of early-stage breast cancer patients to determine whether a significant independent association between Ki-67 and locoregional relapse exists.
Ki-67 staining was conducted on a tissue microarray of 438 patients previously treated with BCT, and expression was analyzed with clinicopathologic features and outcomes from our database.
Ki-67 expression was more prevalent in black patients (37% of black patients vs 17% of white patients, P<.01), younger patients (27% of patients aged ≤50 years vs 15% of patients aged >50 years, P<.01), estrogen receptor (ER)-negative tumors (25% of ER-negative tumors vs 17% of ER-positive tumors, P=.04), human epidermal growth factor receptor 2 (HER2)/neu-positive tumors (35% of HER2-positive tumors vs 18% of HER2-negative tumors, P=.01), and larger tumors (26% of T2 tumors vs 16% of T1 tumors, P=.03). On univariate/multivariate analysis, Ki-67 did not predict for overall survival (74.4% vs 72.6%), cause-specific survival (82.9% vs 82.1%), local relapse-free survival (83.6% vs 88.5%), distant metastasis-free survival (76.1% vs 81.4%), recurrence-free survival (65.5% vs 74.6%), and locoregional recurrence-free survival (81.6% vs 84.7%): P>.05 for all.
Ki-67 appears to be a surrogate marker for aggressive disease and significantly correlates with known prognostic features such as age, race, hormone receptor status, and HER2 status but independently does not predict for locoregional outcomes after BCT when these other prognostic clinicopathologic features are taken into consideration. The independent associations of Ki-67 with race and age appear to be novel to our study.
Ki-67 是一种人类核蛋白，其在增殖细胞中的表达强烈上调，可用于确定克隆细胞群体的生长分数。尽管有一些数据表明 Ki-67 过表达可能与生存或乳房切除术后复发等终点相关，但仍需要进一步阐明其预后意义。特别是在保乳治疗（BCT）后（在这种情况下定义为保乳手术和辅助放疗），Ki-67 是否预测局部区域复发尚未得到研究。本研究的目的是评估早期乳腺癌患者队列中的 Ki-67 表达，以确定 Ki-67 与局部区域复发之间是否存在显著的独立关联。
对先前接受 BCT 治疗的 438 例患者的组织微阵列进行 Ki-67 染色，并通过来自我们数据库的临床病理特征和结果进行分析。
Ki-67 表达在黑人患者中更为普遍（37%的黑人患者 vs 17%的白人患者，P<.01），年轻患者（27%的患者年龄≤50 岁 vs 15%的患者年龄>50 岁，P<.01），雌激素受体（ER）阴性肿瘤（25%的 ER 阴性肿瘤 vs 17%的 ER 阳性肿瘤，P=.04），人表皮生长因子受体 2（HER2）/neu 阳性肿瘤（35%的 HER2 阳性肿瘤 vs 18%的 HER2 阴性肿瘤，P=.01）和更大的肿瘤（26%的 T2 肿瘤 vs 16%的 T1 肿瘤，P=.03）。在单变量/多变量分析中，Ki-67 并不预测总生存率（74.4% vs 72.6%）、无病生存率（82.9% vs 82.1%）、局部无复发生存率（83.6% vs 88.5%）、无远处转移生存率（76.1% vs 81.4%）、无复发生存率（65.5% vs 74.6%）和局部区域无复发生存率（81.6% vs 84.7%）：所有 P>.05。
Ki-67 似乎是一种侵袭性疾病的替代标志物，与已知的预后特征（如年龄、种族、激素受体状态和 HER2 状态）显著相关，但在考虑其他预后临床病理特征时，Ki-67 并不能独立预测 BCT 后的局部区域结局。Ki-67 与种族和年龄的独立关联似乎是我们研究的新发现。
