三阴性乳腺癌亚分型的临床病理研究与预后分析

Clinicopathological study and prognostic analysis of triple-negative breast cancer subtypes

目的基于复旦大学上海肿瘤中心(Fudan University Shanghai Cancer Cente,FUSCC)的免疫组化(immunohistochemica,IHC)分类模型研究不同分子亚型三阴性乳腺癌(triple-negative breast cancer,TNBC)的临床病理及预后差异。方法收集98例于2011年12月至2016年12月在蚌埠医学院第一附属医院接受诊疗的TNBC患者肿瘤组织蜡块,基于IHC分类模型将上述患者分成4组,腔面雄激素受体亚型(luminal androgen recepto,LAR):AR(+);免疫调节亚型(immunomodulatory,IM):AR(-),CD8(+);基底样免疫抑制亚型(basallike immune-suppressed,BLIS):AR(-),CD8(-),FOXC1(+);间充质亚型(mesenchymal-like,MES):AR(-),CD8(-),FOXC1(-),DCLK1(+)。回顾性分析不同组别患者临床病理特征及影响预后的相关因素。结果98例TNBC中,90例可通过IHC分类模型分类,其中LAR型23例(25.56%),IM型29例(32.22%),BLIS型24例(26.67%),MES型14例(15.56%)。4种分型患者之间p53,Ki-67的表达量差异有统计学意义(P<0.05),4种分型患者之间年龄分布、肿瘤长径、淋巴结阳性数目、病理级别、复发转移情况差异无统计学意义(P>0.05),IM型与MES型的预后差异有统计学意义(P<0.05),Cox多因素回归分析提示,淋巴结阳性数目是影响TNBC患者术后5年无病生存期(DFS)和5年总生存期(OS)的独立危险因素(P<0.05)。结论4组TNBC之间Ki-67、p53表达存在差异,IM型具有更低的p53和Ki-67表达率,MES型表现出相对高的Ki-67及p53表达水平,淋巴结阳性个数是影响TNBC患者5年预后的独立危险因素,IM型预后趋势较好,MES型预后较差。

Objective Based on the immunohistochemical(IHC)classification model of Fudan University Shanghai Cancer Center(FUSCC),to study the clinicopathological and prognostic differences of different molecular subtypes of triple-negative breast cancer(TNBC).Methods Paraffin-embedded tumor tissue from 98 TNBC patients,who were treated in the First Affiliated Hospital of Bengbu Medical College from December 2011 to December 2016,were collected.The patients were divided into four groups based on the IHC classification model:LAR subtype(AR+),IM subtype(AR-,CD8+),BLIS subtype(AR-,CD8-,FOXC1+)and MES subtype(AR-,CD8-,FOXC1-,DCLK1+).The clinicopathological features and prognostic factors of different groups were analyzed.Results Among the 98 TNBCs,90 can be classified by IHC classification model,including 23 cases of LAR subtype(25.56%),29 cases of IM subtype(32.22%),24 cases of BLIS subtype(26.67%)and 14cases of MES subtype(15.56%).There were no significant differences in age distribution,tumor diameter,number of positive lymph nodes,pathological grade,recurrence and metastasis among patients with TNBC.There was a significant difference in prognosis between IM subtype and MES subtype.Cox multivariate regression analysis showed that the number of positive lymph nodes was an independent risk factor for 5-year DFS and 5-year OS in TNBC patients.Conclusion There are differences in the expression of Ki-67 and p53 among the four groups of TNBC.The expression of p53 and Ki-67 is lower in IM type,and higher in MES type.The number of positive lymph nodes is an independent risk factor affecting the 5-year survival of TNBC patients.The prognosis of IM subtype is better,while the prognosis of MES subtype is poor.