乳腺癌组织肿瘤细胞和间质免疫细胞程序性死亡配体-1表达与临床病理特征的关系

Correlations of expressions of programmed death ligand-1 in breast cancer cells and interstitial immune cells with clinicopathological features

目的 观察不同分子分型乳腺癌组织肿瘤细胞、间质免疫细胞程序性死亡配体-1(programmed death ligand-1, PD-L1)表达变化,探讨其与乳腺癌临床病理特征的关系。方法 行手术治疗乳腺癌患者370例,其中Luminal A型26例为Luminal A型组,Luminal B型246例为Luminal B型组,人表皮生长因子受体-2(human epidermal growth factor receptor-2, HER-2)过表达型52例为HER-2过表达型组,三阴性46例为三阴性组。取手术切除癌组织,采用免疫组织化学Envision两步法检测肿瘤细胞、间质免疫细胞PD-L1阳性表达率。比较不同分子分型乳腺癌患者以及不同年龄、临床分期、阳性淋巴结数等乳腺癌患者癌组织肿瘤细胞、间质免疫细胞PD-L1阳性表达率。结果 (1)乳腺癌组织间质免疫细胞PD-L1阳性表达率在Luminal B型组、HER-2过表达型组、三阴性组(39.8%、73.1%、65.2%)均高于肿瘤细胞(15.4%、11.5%、17.4%)(P<0.05),在Luminal A型组与肿瘤细胞比较差异无统计学意义(P>0.05)。(2)Luminal A型组、Luminal B型组癌组织间质免疫细胞PD-L1阳性表达率均低于HER-2过表达型组、三阴性组(P<0.05);4组癌组织肿瘤细胞PD-L1阳性表达率比较差异均无统计学意义(P>0.05)。(3)乳腺癌组织间质免疫细胞PD-L1阳性表达率在低密度脂蛋白胆固醇>2.55 mmol/L(52.2%)、核分裂象评分2~3分(55.6%)、Ki-67≥20%(50.5%)、雌激素受体阴性(65.5%)、孕激素受体阴性(61.8%)、HER-2阳性(54.7%)者分别高于低密度脂蛋白胆固醇≤2.55 mmol/L(39.8%)、核分裂象评分1分(29.5%)、Ki-67<20%(22.0%)、雌激素受体阳性(37.7%)、孕激素受体阳性(36.8%)、HER-2阴性(40.8%)者(P<0.05),在不同年龄、临床分期、肿瘤直径、阳性淋巴结数及雄激素受体表达者比较差异均无统计学意义(P>0.05)。(4)乳腺癌组织肿瘤细胞PD-L1阳性表达率在年龄<54岁(18.8%)、临床分期Ⅲ期(26.8%)、阳性淋巴结数≥4个(31.4%)者分别高于年龄≥54岁(11.0%)、临床分期Ⅰ~Ⅱ期(11.1%)、阳性淋巴结数<4个(10.9%)者(P<0.05),在不同低密度脂蛋白胆固醇、肿瘤直径、核分裂象评分及Ki-67、雌激素受体、孕激素受体、雄激素受体、HER-2表达者比较差异均无统计学意义(P>0.05)。结论 Luminal B型、HER-2过表达型、三阴性乳腺癌患者乳腺癌组织间质免疫细胞PD-L1表达高于肿瘤细胞;乳腺癌组织间质免疫细胞PD-L1阳性表达率在低密度脂蛋白胆固醇>2.55 mmol/L、核分裂象评分2~3分、Ki-67≥20%、雌激素受体阴性、孕激素受体阴性、HER-2阳性者增高;癌组织肿瘤细胞PD-L1阳性表达率在年龄<54岁、临床分期Ⅲ期、阳性淋巴结数≥4个者增高。

Objective To observe the changes of programmed death ligand-1(PD-L1) in breast cancer cells and interstitial immune cells in different molecular subtypes, and to investigate the correlations with clinicopathological features. Methods A total of 370 breast cancer patients undergoing surgery were divided into Luminal A group(n=26), Luminal B group(n=246), human epidermal growth factor receptor-2(HER-2) overexpression group(n=52), and triple-negative group(n=46). The positive rates of PD-L1 in breast cancer cells and interstitial immune cells were detected by immunohistochemistry Envision, and were compared among patients in different molecular types and in patients with different ages, clinical stages and numbers of positive lymph nodes. Results The positive rates of PD-L1 were higher in interstitial immune cells(39.8%,73.1%,65.2%)than those in cancer cells(15.4%,11.5%,17.4%)in Luminal B group,HER-2overexpression group and triple-negative group(P<0.05),and showed no significant differences in Luminal A group(P>0.05).The positive rates of PD-L1in interstitial immune cells were lower in Luminal A group and Luminal B group than those in HER-2overexpression group and triple-negative group(P<0.05),and showed no significant differences among four groups(P>0.05).The positive rates of PD-L1in interstitial immune cells were higher in patients with low-density lipoprotein cholesterol(LDL-C)>2.55mmol/L(52.2%),mitotic score 2-3(55.6%),Ki-67 ≥20%(50.5%),estrogen receptor(ER)negative(65.5%),progesterone receptor(PR)negative(61.8%)and HER-2positive(54.7%)than those in patients with LDL-C ≤2.55mmol/L(39.8%),mitotic score 1(29.5%),Ki-67 <20%(22.0%),ER positive(37.7%),PR positive(36.8%)and HER-2negative(40.8%)(P<0.05),and showed no significant differences in patients with different ages,clinical stages,tumor diameters,numbers of positive lymph nodes and androgen receptor expressions(P>0.05).The positive rates of PD-L1in cancer cells were higher in patients with age <54years(18.8%),clinical stage Ⅲ (26.8%)and positive lymph nodes ≥4(31.4%)than those in patients with age ≥54years(11.0%),clinical stage Ⅰ-Ⅱ (11.1%)and positive lymph nodes<4(10.9%)(P<0.05),and showed no significant differences in patients with different LDL-C levels,tumor diameters,mitotic scores,and levels of Ki-67,ER,PR,androgen receptor and HER-2(P>0.05).Conclusions The positive rates of PD-L1in interstitial immune cells are higher than those in cancer cells in patients with Luminal B,HER-2overexpression and triple-negative breast cancer,and increase significantly in patients with LDL-C >2.55 mmol/L,mitotic score 2-3,Ki-67≥20%,ER negative,PR negative and HER-2positive.The positive rates of PD-L1in cancer cells are high in patients aged younger than 54years,in clinical stageⅢ and number of positive lymph nodes≥4.