Abstract

Abstract Background: Ki-67 has been increasingly used as a prognostic marker in spite of debates on the evaluation methods and inconsistent results on its clinical values. CKAP2 is a microtubule-associated protein which plays key roles in microtubule assembly and disassembly. In the present study, the clinical significance of CKAP2-positive cells was evaluated and compared with the results of Ki-67 positive cells. Methods: A total of 579 early breast cancer patients who underwent surgery at the National Cancer Center Hospital between 2001 and 2005 were accrued. The proliferation activity was measured by CKAP2-positive cell count (CPCC) and Ki-67 labeling index (Ki-67 LI) using CKAP2 and Ki-67 antibodies, respectively, by immunohistochemcial staining on FFPE tumor tissue. The correlation of CPCC or Ki-67 LI with recurrence free survival (RFS) was analyzed. The immunofluorescent staining was performed on HeLa cells after synchronization by double thymidine block to compare the patterns between CKAP2 and Ki-67. Results: The CPCC (median, 8 with the range of 0- 170) and Ki-67 LI (median, 10.2 with the range of 0%- 91.7%) were highly correlated (R = 0.754, P < 0.001). While CPCC was marginally significant in multivariate analysis for RFS in all cases, it was a significant variable for RFS in the subset analysis with HER2-negative luminal breast cancer patients (HR, 3.154; 95% CI, 1.154-10.693; P = 0.027). On the contrary, Ki-67 LI failed to show any correlation with RFS in all or any subgroups. In the analysis on HeLa cells, CKAP2 staining was more specific to cells in metaphase than Ki-67 staining. Conclusions: CPCC can be an independent prognostic factor specifically in a HER2-negative luminal type of breast cancer. In addition, CPCC appears to be superior to Ki-67 LI as a survival indicator which may be related to the restricted expression pattern of CKAP2 in metaphase cells. Further study is warranted. Citation Format: Sim SH, Bae C-D, Kwon Y, Park IH, Lee KS, Jung S-Y, Lee S, Kang H-S, Lee ES, Kim H-S, Hong K-M, Ro J. CKAP2 (cytoskeleton associated protein 2) is a new prognostic marker in HER2-negative luminal breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-25.

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