Chen Zonglin, Chen Xianyu, Zhou Enxiang, Chen Ganlong, Qian Ke, Wu Xia, Miao Xiongying, Tang Zhonghua
Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha, China.
Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, China.
PLoS One. 2014 Apr 17;9(4):e95475. doi: 10.1371/journal.pone.0095475. eCollection 2014.
The prognostic effect of tumor infiltrating CD8+ cytotoxic lymphocytes (CTLs) in breast cancer is controversial. We analyzed the association between CD8+ CTLs and survival of untreated node-negative breast cancer patients.
CD8+ CTLs infiltrate was evaluated by immunostaining in a cohort of 332 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of CD8+ CTLs for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate analysis and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 expression and human epidermal growth factor receptor 2 (HER-2) status.
285 (85.8%) patients showed strong CD8+ CTLs infiltrate positive status. Univariate analysis showed that CD8+ CTLs had statistically significant association with DFS (P = 0.004, hazard ratio [HR] = 0.454, 95% confidence interval [CI] = 0.265-0.777) and OS (P = 0.014, HR = 0.430, 95% CI = 0.220-0.840) in the entire cohort. The significance of CD8+ CTLs was especially strong in ER negative, HER-2 negative and ER, PR, HER-2 triple-negative breast cancers. In Kaplan-Meier analysis, CD8+ CTLs had significant effect on prognosis of patients (Log-rank test: P = 0.003 for DFS and P = 0.011 for OS), independent of established clinical factors for DFS (P = 0.002, HR = 0.418, 95% CI = 0.242-0.724) as well as for OS (P = 0.009, HR = 0.401, 95% CI = 0.202-0.797).
肿瘤浸润性CD8+细胞毒性淋巴细胞（CTLs）在乳腺癌中的预后作用存在争议。我们分析了CD8+ CTLs与未经治疗的淋巴结阴性乳腺癌患者生存之间的关联。
通过免疫染色评估了332例淋巴结阴性乳腺癌患者队列中的CD8+ CTLs浸润情况，中位随访时间为152个月。采用Kaplan-Meier生存分析以及单因素分析和多因素Cox分析评估CD8+ CTLs对无病生存期（DFS）和乳腺癌特异性总生存期（OS）的预后意义，分析时对诊断年龄、pT分期、组织学分级、雌激素受体（ER）状态、孕激素受体（PR）状态、Ki-67表达和人表皮生长因子受体2（HER-2）状态进行了校正。
285例（85.8%）患者显示CD8+ CTLs浸润强阳性状态。单因素分析显示，在整个队列中，CD8+ CTLs与DFS（P = 0.004，风险比[HR] = 0.454，95%置信区间[CI] = 0.265 - 0.777）和OS（P = 0.014，HR = 0.430，95% CI = 0.220 - 0.840）具有统计学显著关联。CD8+ CTLs的意义在ER阴性、HER-2阴性以及ER、PR、HER-2三阴性乳腺癌中尤为显著。在Kaplan-Meier分析中，CD8+ CTLs对患者预后有显著影响（对数秩检验：DFS的P = 0.003，OS的P = 0.011），独立于既定的DFS临床因素（P = 0.002，HR = 0.418，95% CI = 0.242 - 0.724）以及OS临床因素（P = 0.009，HR = 0.401，95% CI = 0.202 - 0.797）。
