乳腺癌原发灶与转移灶间质浸润免疫细胞PD-L1的表达异质性分析
Heterogeneity in PD-L1 expression on infiltrating immune cells between the primary and metastatic breast cancers
摘要目的:探讨乳腺癌原发灶与转移灶间质浸润免疫细胞程序性死亡因子配体1(PD-L1)的表达,并探讨其与临床病理参数的关系。方法:收集河北医科大学第四医院2010年1月至2018年12月140例乳腺癌原发灶及其配对转移灶患者资料。应用免疫组织化学法检测PD-L1在乳腺癌原发灶及转移灶间质浸润免疫细胞中的表达情况。一致性分析采用Kappa检验,差异性分析采用McNemar检验。结果:140例中52例有淋巴结转移,88例有远处转移(包括肝35例、肺21例、胸壁13例、骨11例、脑6例、小肠1例、眼球1例)。乳腺癌原发灶与转移灶间质浸润免疫细胞PD-L1表达的总体一致率为72.9%(κ=0.441)。乳腺癌原发灶与配对淋巴结转移灶、总体远处转移灶PD-L1表达一致率分别为75.0%(κ=0.472)和71.6%(κ=0.426)。但乳腺癌原发灶与配对肺转移灶间质浸润免疫细胞PD-L1的表达不一致率为28.6%(6/21),差异有统计学意义( P=0.031)。乳腺癌原发灶间质免疫细胞PD-L1的表达与患者肿瘤大小、组织学分级、脉管瘤栓、淋巴结转移和Ki-67阳性指数有明显相关性( P<0.05),淋巴结转移是PD-L1表达的独立影响因素( P<0.05);乳腺癌转移灶间质浸润免疫细胞PD-L1的表达与ER的表达有明显相关性( P<0.05)。 结论:乳腺癌原发灶与转移灶PD-L1表达总体一致性一般,与配对肺转移灶表达存在差异。需要重新评估PD-L1在远处转移的活检组织中的表达,以优化PD-L1的临床应用。
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abstractsObjective:To investigate the expression difference in PD-L1 on mesenchymal infiltrating immune cells between the primary and metastatic breast cancers, and to explore its relationship with clinicopathological parameters.Methods:All cases of primary breast cancer and their matched metastases diagnosed at the Fourth Hospital of Hebei Medical University between January 2010 and December 2018 were included. Immunohistochemistry (IHC) was used to detect the expression of PD-L1 (SP142) in interstitial infiltrating immune cells, and the expression of ER, PR, HER2 and Ki-67 in primary and matched metastases was detected. Statistical software SPSS 24.00 was used for statistical analysis. Kappa test was used for concordance/agreement analysis and McNemar test for difference analysis.Results:Among the 140 identified primary breast cancers, there were 52 cases with matched lymph node metastasis, 88 cases with distant metastasis, including 35 cases with liver metastasis, 21 cases with lung metastasis, 13 cases with chest wall metastasis, 11 cases with bone metastasis, 6 cases with brain metastasis, 1 case with small intestine metastasis, and 1 case with eyeball metastasis. The overall concordance rate of the PD-L1 expression on mesenchymal immune cells between primary breast cancer and paired metastatic breast cancer was 72.9% (κ=0.441). The concordance rate of PD-L1 expression between primary breast cancers and paired lymph node metastases, and that between primary breast cancers and distant metastases were 75.0% (κ=0.472) and 71.6% (κ=0.472), respectively. The inconcordance rate of interstitial immune cell PD-L1 expression between primary breast cancer and matched lung metastasis was 28.6%(6/21), and the difference was statistically significant ( P=0.031). The expression of PD-L1 in mesenchymal immune cells of primary breast cancer was significantly correlated with tumor size, histological grade, vascular invasion, lymph node metastasis, and Ki-67 index ( P<0.05). The PD-L1 expression was independently associated with lymph node metastasis ( P<0.05), while the expression of PD-L1 in metastatic breast cancer interstitial immune cells was significantly related to the expression of ER ( P<0.05). Conclusions:The expression of PD-L1 in the primary breast cancer is moderately concordant with that in paired metastases, but different from that in paired lung metastases. Therefore, the expression of PD-L1 in distant metastasis needs to be re-evaluated to optimize the treatment outcomes of PD-L1 based therapy.
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