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PLoS One ; 12(8): e0182107, 2017.
Article in English | MEDLINE | ID: mdl-28771517

ABSTRACT

BACKGROUND: Recently, we reported cytoskeleton-associated protein2 (CKAP2) as a possible new prognostic breast cancer marker. However, it has not yet been applied in clinic. Therefore, clinical significance of CKAP2 was evaluated in comparison with that of Ki-67 in a cohort of breast cancer patients, and the expression difference was analyzed in cell cycle-arrested cancer and fibroblast cells. METHODS: A total of 579 early breast cancer patients who underwent surgery at the National Cancer Center Hospital in Korea between 2001 and 2005 were accrued. CKAP2-positive cell count (CPCC) and Ki-67 labeling index (Ki-67LI) were evaluated by immunohistochemcal staining. The immunocytochemical staining patterns of CKAP2 and Ki-67 were analyzed in HeLa and human fibroblast cells after synchronization by double thymidine block. RESULTS: Although there was a significant correlation (R = 0.754, P < 0.001) between CPCC and Ki-67LI, only CPCC was correlated with DFS in overall population (HR, 2.029; 95% CI, 1.012-4.068; P = 0.046) and HER2-negative luminal subgroup (HR, 3.984; 95% CI, 1.350-11.762; P = 0.012) by multivariate analysis. In immunocytochemical staining, more than 50% of serum-starved or non-mitotic cell phase HeLa cells were positive for Ki-67, in comparison to the low CKAP2-positivity, which might explain the prognostic difference between CPCC and Ki-67LI. CONCLUSIONS: The current study showed that CPCC but not Ki-67LI is an independent prognostic indicator in early breast cancer, more specifically in HER2-negative luminal breast cancer. The difference between two markers may be related to the lower background expression of CKAP2 in cancer cells.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Cytoskeletal Proteins/metabolism , Gene Expression Regulation, Neoplastic , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cells, Cultured , Cytoskeletal Proteins/genetics , Disease-Free Survival , Female , Fibroblasts/metabolism , HeLa Cells , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Ki-67 Antigen/metabolism , Middle Aged , Multivariate Analysis , Prognosis , Receptor, ErbB-2/metabolism
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