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三阴性乳腺癌(triple negative breast cancer,TNBC)特指雌激素受体(ER)、孕激素受体(PR)表达均为阴性,且人表皮生长因子受体(HER-2)表达缺失的一种复杂难治的乳腺癌亚型[1]。在ECOG-2100试验中,TNBC的发生率为32%,在RIBBOn-1和AVADO试验中,TNBC的发生率分别为23%和22%。TNBC侵袭性高,易发生内脏转移和神经系统转移[2]。除了手术、化疗、放疗,缺乏有效的靶向治疗,同时由于TNBC表现出来的临床和遗传特征,有效低毒的化疗方案选择有限,有必要寻找到新的评估预后的方法和治疗手段。有报道[3]称在黑素瘤、乳腺癌、结肠癌中肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TILs)的存在与对免疫疗法的增强反应有关,肿瘤淋巴细胞浸润和活化是宿主抗肿瘤免疫应答的关键组分,是预后良好的标志。本研究主要探讨TILs在TNBC中的浸润情况及其与预后的关系。现作报道。
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根据TNBC标本原发灶中基质中TILs(STILs)和癌巢内TILs(ITILs)的表达情况,按照浸润水平的高低进行统计分类,整体TILs取ITILs和STILs的平均值见表 1。
分值/% STILs ITILs 整体TILs 0~10 7(15.6) 5(11.1) 5(11.1) 11~40 26(57.8) 27(60.0) 24(53.3) 41~100 12(26.6) 13(28.9) 16(35.6) 表 1 TILs在TNBC基质和癌巢中的表达分布情况[n;百分率(%)]
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用不同病人的临床病理参数作为自变量,用OS及DFS作为因变量,进行COX单因素分析,结果显示,淋巴结阳性的个数多少和临床分期是OS、DFS的相关因素;STILs、ITILs、ITILs也是OS、DFS的相关因素(见表 2)。
因素 OS DFS HR 95%CI P HR 95%CI P 肿瘤直径/cm (≤2 v >2~5 v>5) 1.672 0.798~3.526 >0.05 1.735 0.789~3.462 >0.05 阳性淋巴结 (0 v 1~3 v 4~9 v ≥10) 2.081 1.441~2.996 < 0.05 2.201 1.552~3.122 < 0.05 手术方式 (根治术v保乳术) 0.478 0.162~1.798 >0.05 0.532 0.125~1.479 >0.05 临床分期 (ⅠvⅡv Ⅲ) 3.102 1.763~5.675 < 0.05 3.124 1.581~5.492 < 0.05 Ki-67/% (< 20 v ≥20) 22.781 0.027~45.778 >0.05 23.145 0.132~76.658 >0.05 组织学分级 (1 v 2 v 3) 2.006 0.821~4.337 >0.05 1.796 0.554~6.143 >0.05 肿块位置 (左v右v双侧) 1.664 0.864~3.963 >0.05 1.667 0.895~4.001 >0.05 治疗方案 (0 v TEC v EC-T v TC v其他) 1.248 0.649~1.475 >0.05 0.886 0.712~1.236 >0.05 STILs (0~10 v 11~40 v 41~100) 0.043 0.018~0.998 < 0.05 0.034 0.021~0.093 < 0.05 ITILs (≤10 v 10~40 v >40) 0.505 0.017~0.992 < 0.05 0.029 0.014~0.884 < 0.05 TILs (≤10 v 10~40 v >40) 0.045 0.021~0.120 < 0.05 0.207 0.017~0.091 < 0.05 表 2 TNBC OS和DFS影响因素的单因素分析
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把P < 0.05认定为有统计学意义,把COX单因素分析筛选出来的5个指标进一步进行多因素分析,可以得出以下结论:STILs、ITILs、ITIL是OS、DFS的保护因素。STILs、ITILs、ITIL的表达水平越高,病人的OS和DFS越高,病人预后越好(见表 3)。
因素 OS DFS HR 95%CI P HR 95%CI P 阳性淋巴结个数 (0 v 1~3 v 4~9 v ≥10) 1.205 0.713~2.681 >0.05 1.428 0.568~2.873 >0.05 临床分期 (ⅠvⅡv Ⅲ) 1.901 0.756~5.958 >0.05 1.590 0.687~5.002 >0.05 STILs (≤10 v 10~40 v >40) 0.048 0.058~0.483 < 0.05 0.059 0.009~0.469 < 0.05 ITILs (≤10 v 10~40 v >40) 0.043 0.081~0.304 < 0.05 0.401 0.007~0.183 < 0.05 TILs (≤10 v 10~40 v >40) 0.684 0.082~0.401 < 0.05 0.056 0.007~0.612 < 0.05 表 3 TNBC OS和DFS影响因素的多因素分析
肿瘤浸润淋巴细胞在三阴性乳腺癌中的浸润情况及意义
Infiltration and significance of tumor infiltrating lymphocytes in triple negative breast cancer
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摘要:
目的对三阴性乳腺癌(TNBC)病人原发灶癌巢和间质中的肿瘤浸润淋巴细胞(TILs)进行计数,分析TILs在TNBC中的浸润情况及其与临床预后的关系。 方法选取来自蚌埠医学院第一附属医院的TNBC病人45例,通过HE染色来计数TILs在原发灶癌巢和间质中的分布情况,根据相应的临床资料和病理特征分析TILs和临床预后之间的关系。 结果基质中TILs(STILs)、癌巢内TILs(ITILs)、整体TILs是TNBC病人总生存率(OS)和无病生存率(DFS)的保护因素,阳性淋巴结数目和临床分期是TNBC病人OS和DFS的危险因素。STILs、ITILs、TILs浸润水平越高病人预后越好。 结论STILs、ITILs、TILs是TNBC病人的独立预后影响因素。 Abstract:ObjectiveTo count the tumor infiltrating lymphocytes(TILs) in the primary tumor nests and stroma in patients with triple negative breast cancer(TNBC), and analyze the infiltration of TILs in TNBC and its relationship with clinical prognosis. MethodsForty-five patients with TNBC were selected from The First Affiliated Hospital of Bengbu Medical College. The expression of TILs in primary tumor nests and stroma were counted by HE staining, and the relationship between TILs and clinical prognosis was analyzed according to the corresponding clinical data and pathological features. ResultsThe stromal TILs(STILs), intracellular TILs(ITILs) and global TILs were the protective factors of overall survival(OS) and disease-free survival(DFS) in TNBC patients. The number of positive lymph nodes and clinical stage were the risk factors of OS and DFS in TNBC patients. The higher the infiltration levels of STILs, ITILs and TILs were, the better the prognosis was. ConclusionsThe levels of STILs, ITILs and TILs are the dependent prognostic factors in patients with TNBC. -
表 1 TILs在TNBC基质和癌巢中的表达分布情况[n;百分率(%)]
分值/% STILs ITILs 整体TILs 0~10 7(15.6) 5(11.1) 5(11.1) 11~40 26(57.8) 27(60.0) 24(53.3) 41~100 12(26.6) 13(28.9) 16(35.6) 表 2 TNBC OS和DFS影响因素的单因素分析
因素 OS DFS HR 95%CI P HR 95%CI P 肿瘤直径/cm (≤2 v >2~5 v>5) 1.672 0.798~3.526 >0.05 1.735 0.789~3.462 >0.05 阳性淋巴结 (0 v 1~3 v 4~9 v ≥10) 2.081 1.441~2.996 < 0.05 2.201 1.552~3.122 < 0.05 手术方式 (根治术v保乳术) 0.478 0.162~1.798 >0.05 0.532 0.125~1.479 >0.05 临床分期 (ⅠvⅡv Ⅲ) 3.102 1.763~5.675 < 0.05 3.124 1.581~5.492 < 0.05 Ki-67/% (< 20 v ≥20) 22.781 0.027~45.778 >0.05 23.145 0.132~76.658 >0.05 组织学分级 (1 v 2 v 3) 2.006 0.821~4.337 >0.05 1.796 0.554~6.143 >0.05 肿块位置 (左v右v双侧) 1.664 0.864~3.963 >0.05 1.667 0.895~4.001 >0.05 治疗方案 (0 v TEC v EC-T v TC v其他) 1.248 0.649~1.475 >0.05 0.886 0.712~1.236 >0.05 STILs (0~10 v 11~40 v 41~100) 0.043 0.018~0.998 < 0.05 0.034 0.021~0.093 < 0.05 ITILs (≤10 v 10~40 v >40) 0.505 0.017~0.992 < 0.05 0.029 0.014~0.884 < 0.05 TILs (≤10 v 10~40 v >40) 0.045 0.021~0.120 < 0.05 0.207 0.017~0.091 < 0.05 表 3 TNBC OS和DFS影响因素的多因素分析
因素 OS DFS HR 95%CI P HR 95%CI P 阳性淋巴结个数 (0 v 1~3 v 4~9 v ≥10) 1.205 0.713~2.681 >0.05 1.428 0.568~2.873 >0.05 临床分期 (ⅠvⅡv Ⅲ) 1.901 0.756~5.958 >0.05 1.590 0.687~5.002 >0.05 STILs (≤10 v 10~40 v >40) 0.048 0.058~0.483 < 0.05 0.059 0.009~0.469 < 0.05 ITILs (≤10 v 10~40 v >40) 0.043 0.081~0.304 < 0.05 0.401 0.007~0.183 < 0.05 TILs (≤10 v 10~40 v >40) 0.684 0.082~0.401 < 0.05 0.056 0.007~0.612 < 0.05 -
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