Carbognin Luisa, Sperduti Isabella, Brunelli Matteo, Marcolini Lisa, Nortilli Rolando, Pilotto Sara, Zampiva Ilaria, Merler Sara, Fiorio Elena, Filippi Elisa, Manfrin Erminia, Pellini Francesca, Bonetti Franco, Pollini Giovanni Paolo, Tortora Giampaolo, Bria Emilio
Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, P.le L.A. Scuro 10, 37124, Verona, Italy.
Biostatistics, Regina Elena National Cancer Institute, Rome, Italy.
J Exp Clin Cancer Res. 2016 Mar 22;35:50. doi: 10.1186/s13046-016-0325-z.
The aim of this analysis was to investigate the potential impact of Ki67 assay in a series of patients affected by early stage invasive lobular carcinoma (ILC) undergone surgery.
Clinical-pathological data were correlated with disease-free and overall survival (DFS/OS). The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate appropriate cut-offs. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed to assess the interaction between 'pure' or 'mixed' histology ILC and Ki67.
At a median follow-up of 67 months, 10-years DFS and OS of 405 patients were 67.8 and 79.8%, respectively. Standardized Log-Rank statistics identified 2 optimal cut-offs (6 and 21%); 10-years DFS and OS were 75.1, 66.5, and 30.2% (p = 0.01) and 84.3, 76.4 and 59% (p = 0.003), for patients with a Ki67 < 6%, between 6 and 21%, and >21%, respectively. Ki67 and lymph-node status were independent predictor for longer DFS and OS at the multivariate analysis, with radiotherapy (for DFS) and age (for OS). Ki67 highly replicated at the internal cross-validation analysis (DFS 85%, OS 100%). The STEPP analysis showed that DFS rate decreases as Ki67 increases and those patients with 'pure' ILC performed worse than 'mixed' histology.
Despite the retrospective and exploratory nature of the study, Ki67 was able to significantly discriminate the prognosis of patients with ILC, and the effect was more pronounced for patients with 'pure' ILC.
本分析旨在研究Ki67检测对一系列接受手术的早期浸润性小叶癌（ILC）患者的潜在影响。
将临床病理数据与无病生存期和总生存期（DFS/OS）相关联。对Ki67连续变量应用最大选择对数秩统计分析以估计合适的临界值。进行亚组治疗效应模式图（STEPP）分析以评估“纯”或“混合”组织学ILC与Ki67之间的相互作用。
在中位随访67个月时，405例患者的10年DFS和OS分别为67.8%和79.8%。标准化对数秩统计确定了2个最佳临界值（6%和21%）；对于Ki67<6%、6%至21%和>21%的患者，10年DFS分别为75.1%、66.5%和30.2%（p=0.01），10年OS分别为84.3%、76.4%和59%（p=0.003）。在多因素分析中，Ki67和淋巴结状态是DFS和OS更长的独立预测因素，此外放疗（对于DFS）和年龄（对于OS）也是。Ki67在内部交叉验证分析中高度重复（DFS为85%，OS为100%）。STEPP分析表明DFS率随Ki67增加而降低，且“纯”ILC患者的表现比“混合”组织学患者更差。
尽管本研究具有回顾性和探索性，但Ki67能够显著区分ILC患者的预后，且对“纯”ILC患者的影响更为明显。
