肿瘤相关巨噬细胞CD68蛋白与乳腺癌临床病理特征对新辅助化疗疗效和预后的影响

Effects of tumor-associated macrophage CD68 protein and clinicopathologic features of breast cancer on efficacy and prognosis of neoadjuvant chemotherapy

目的:分析肿瘤相关巨噬细胞CD68蛋白与乳腺癌临床病理特征对新辅助化疗(neoadjuvant chemotherapy,NCT)疗效和预后的影响。方法:选取2013年1月至2017年1月于南京大学医学院附属鼓楼医院收治的局部晚期乳腺癌患者172例为研究对象,免疫组织化学检测癌组织中ER,HGR2,Ki-67以及CD68的表达,所有患者NCT后1个月内进行手术,分析临床病理学参数和病理完全缓解率(pathologic complete response,pCR)之间的关系。结果:CD68表达和ER呈负相关(r=-0.129,P=0.018),CD68表达和HER2(r=0.211,P=0.011)、Ki-67(r=0.195,P=0.013)以及肿瘤直径(r=0.315,P=0.007)呈明显正相关,而CD68和患者的年龄、绝经状况以及淋巴结是否出现转移无明显关系(P>0.05);ER阴性组pCR率(25.95%)明显高于阳性组(7.81%),差异具有统计学意义(P<0.05);Ki-67高表达组pCR率(32.39%)明显高于低表达组(9.90%),差异具有统计学意义(P<0.05);CD68高表达组pCR率(24.11%)明显高于低表达组(10.00%),差异具有统计学意义(P<0.05);经过化疗后,有131例患者(72.16%)CD68表达下降,下降组pCR率为24.43%(32/131),未下降组(无变化或者出现上升)患者的pCR率为2.44%(1/41),提示化疗后CD68变化与化疗疗效相关,差异具有统计学意义(P<0.05);各分子亚型和绝经状况、化疗前肿瘤直径、疗效以及化疗前CD68表达明显相关(P<0.05),而与年龄、淋巴结转移不相关(P>0.05);化疗前,CD68低表达组总生存时间(overall survival,OS)和无病生存时间(disease-free survival,DFS)均优于CD68高表达组,差异具有统计学意义(P<0.05)。化疗后CD68下降组OS和DFS均较未下降组延长,差异具有统计学意义(P<0.05)。COX多因素回归分析结果显示化疗前Ki-67、CD68、化疗后CD68变化是影响DFS的独立危险因素。结论:CD68高表达者对化疗更为敏感,但预后差,化疗前Ki-67、CD68、化疗后CD68变化是影响DFS的独立危险因素,Ki-67,ER,HGR2以及CD68分子亚型可以作为NCT疗效的预测指标。

Objective:to analyze the effect of CD68 protein of tumor-associated macrophage and the clinicopathological features of breast cancer on the efficacy and prognosis of neoadjuvant chemotherapy(NCT).Methods:In January 2013 to January 2017,172 cases of patients with Locally advanced breast cancer in the Affiliated Drum Tower Hospital of Medical College of Nanjing University were selected as the research objects.ER,HGR2,Ki-67,and the expression of CD68 were detected by immunohistochemical.All patients were given surgery within 1 month after NCT.Clinical pathology analysis parameters and pathological complete response rate(pathologic complete response,pCR)relationship was analysed.Results:CD68 expression was negatively correlated with ER(r=?0.129,P=0.018),CD68 expression was positively correlated with HER2(r=0.211,P=0.011),Ki-67(r=0.195,P=0.013)and tumor diameter(r=0.315,P=0.007),while there was no significant correlation between CD68 and patient age,menopausal status and lymph node metastasis(P>0.05).The pCR rate of ER negative group(25.95%)was significantly higher than that of the positive group(7.81%)(P<0.05).The pCR rate(32.39%)of the Ki-67 group with high expression was significantly higher than that of the group with low expression(9.90%)(P<0.05).The pCR rate(24.11%)of the group with high CD68 expression was significantly higher than that of the group with low expression(10.00%)(P<0.05).After chemotherapy,the expression of CD68 decreased,the pCR ratewas 24.43%(32/131)in the decreasing group,and the pCR rate was 2.44%(1/41)in the nondecreasing group(no change or rise),suggesting that the change of CD68 after chemotherapy was correlated with the efficacy of chemotherapy(P<0.05).The molecular subtypes were significantly correlated with menopausal status,tumor diameter before chemotherapy,efficacy and CD68 expression before chemotherapy(P<0.05),but not with age or lymph node metastasis(P>0.05).Before chemotherapy,both OS and DFS in the group with low CD68 expression were superior to the group with low and high CD68 expression(P<0.05).After chemotherapy,both OS and DFS in the CD68 decreased group were longer than those in the decreasing group(P<0.05).COX multivariate regression analysis showed that the changes of ki-67,CD68 before chemotherapy and CD68 after chemotherapy were independent risk factors affecting DFS.Conclusion:High expression of CD68 was more sensitive to chemotherapy,but the prognosis was poor.Changes of ki-67,CD68 and CD68 after chemotherapy are independent risk factors affecting DFS,and ki-67,ER,HGR2,CD68 and molecular subtypes can be used as predictors of the efficacy of NCT.