Abstract
BackgroundRecently, 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.MethodsA 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.ResultsAlthough 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.ConclusionsThe 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.
Highlights
Proliferation activity of cancer cells has long been suggested as a prognostic indicator in breast cancer [1], that genes related to the cell proliferation were incorporated in microarray gene sets for the prognostic prediction [2, 3]
There was a significant correlation (R = 0.754, P < 0.001) between CKAP2-positive cell count (CPCC) and Ki67LI, only CPCC was correlated with Disease free survival (DFS) in overall population (HR, 2.029; 95% confidence intervals (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
More than 50% of serum-starved or non-mitotic cell phase HeLa cells were positive for Ki-67, in comparison to the low cytoskeleton-associated protein2 (CKAP2)-positivity, which might explain the prognostic difference between CPCC and Ki-67 labeling index (Ki-67LI)
Summary
Proliferation activity of cancer cells has long been suggested as a prognostic indicator in breast cancer [1], that genes related to the cell proliferation were incorporated in microarray gene sets for the prognostic prediction [2, 3]. Mitotic index, which is measured by direct counting of mitotic cells, has been one of the most reliable prognostic markers in breast cancer [6, 7]. It has not been widely applied in the clinic, and useful immunohistochemical markers for the proliferation activity are in need. We reported cytoskeleton-associated protein (CKAP2) as a possible new prognostic breast cancer marker. It has not yet been applied in clinic. 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
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