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Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy

Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy

Authors :
Masako Ikemura
Kanako Inaba
Hideki Ishihara
Daichi Maeda
Tomoyuki Fujii
Tomohiko Fukuda
Masahi Fukayama
Yoko Matsumoto
Kei Kawana
Katsutoshi Oda
Daisuke Aoki
Tomoko Kashiyama
Kenbun Sone
Tetsu Yano
Yutaka Osuga
Osamu Wada-Hiraike
Takahide Arimoto
Yuji Ikeda
Aki Miyasaka
Source :
British Journal of Cancer
Publication Year :
2015
Publisher :
Springer Science and Business Media LLC, 2015.

Abstract

Background: Pathologically low-risk endometrial cancer patients do not receive postoperative treatment; however, 10–15% of these patients show recurrence with poor prognosis. We evaluated the clinical importance of cyclin-dependent kinase 4/6 (CDK4/6) activity, and its significance as a novel biomarker for the prognosis and chemo-sensitivity of endometrioid endometrial carcinoma (EEC). Methods: Cyclin-dependent kinase 4/6 expression and enzyme activity in 109 tumour samples from patients with EEC were examined with a cell-cycle profiling (C2P) assay. CDK4/6-specific activity (CDK4/6SA) was determined, and its relationship with clinicopathological factors and expression of Ki-67 was analysed. Results: CDK4/6-specific activity was significantly correlated with Ki-67 (P=0.035), but not with any other clinicopathological characteristics. CDK4/6SA was significantly higher (P=0.002) in pathologically low-risk patients (not receiving adjuvant chemotherapy, n=74) than in intermediate- or high-risk patients (receiving adjuvant chemotherapy, n=35). In addition, patients with high CDK4/6SA (>3.0) showed significantly (P=0.024) shorter progression-free survival (PFS) than those with low CDK4/6SA (15%) was robustly associated with shorter PFS (P=0.015), and this combination was an independent poor prognostic factor in the low-risk group. Inversely, in the intermediate-/high-risk group, patients with high CDK4/6SA had a tendency of a more favourable prognosis compared with patients with low CDK4/6SA (P=0.063). Conclusions: CDK4/6-specific activity can be used as a biomarker to predict prognosis and, possibly, chemo-sensitivity. The combination of Ki-67 expression might strengthen the clinical usefulness of CDK4/6SA as a biomarker.

Details

ISSN :
15321827 and 00070920
Volume :
113
Database :
OpenAIRE
Journal :
British Journal of Cancer
Accession number :
edsair.doi.dedup.....60f6a43f284b33ef6c9e848b297b5c87
Full Text :
https://doi.org/10.1038/bjc.2015.369