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

Yuji Ikeda, Katsutoshi Oda, Hideki Ishihara, Osamu Wada-Hiraike, Aki Miyasaka, Tomoko Kashiyama, Kanako Inaba, Tomohiko Fukuda, Kenbun Sone, Yoko Matsumoto, Takahide Arimoto, Daichi Maeda, Masako Ikemura, Masahi Fukayama, Kei Kawana, Tetsu Yano, Daisuke Aoki, Yutaka Osuga, Tomoyuki Fujii

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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.

Original languageEnglish
Pages (from-to)1477-1483
Number of pages7
JournalBritish Journal of Cancer
Volume113
Issue number10
DOIs
Publication statusPublished - 2015 Nov 17

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Keywords

  • chemo-sensitivity
  • cyclin-dependent kinase
  • endometrial cancer
  • Ki-67 expression
  • low risk

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ikeda, Y., Oda, K., Ishihara, H., Wada-Hiraike, O., Miyasaka, A., Kashiyama, T., Inaba, K., Fukuda, T., Sone, K., Matsumoto, Y., Arimoto, T., Maeda, D., Ikemura, M., Fukayama, M., Kawana, K., Yano, T., Aoki, D., Osuga, Y., & Fujii, T. (2015). Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy. British Journal of Cancer, 113(10), 1477-1483. https://doi.org/10.1038/bjc.2015.369