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Tumor-related mutations in cell-free DNA in pre-operative plasma as a prognostic indicator of recurrence in endometrial cancer
  1. Daisuke Shintani1,
  2. Taro Hihara2,
  3. Aiko Ogasawara1,
  4. Sho Sato1,
  5. Akira Yabuno1,
  6. Kenji Tai2,
  7. Keiichi Fujiwara1,
  8. Keisuke Watanabe2 and
  9. Kosei Hasegawa1
  1. 1 Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan
  2. 2 Tsukuba Research Laboratories, Eisai Inc. Ltd, Tsukuba, Ibaraki, Japan
  1. Correspondence to Professor Kosei Hasegawa, Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka 350-1298, Saitama, Japan; koseih{at}saitama-med.ac.jp

Abstract

Objectives Circulating tumor DNA (ctDNA) has potential as a basis for understanding the molecular features of a tumor non-invasively and for use as a diagnostic, prognostic, and disease-monitoring marker. The aim of this study was to evaluate the clinical roles of ctDNA in patients with endometrial cancer.

Methods Since PIK3CA and KRAS are among the most common mutated genes in endometrial cancer, somatic mutations of these genes were investigated in tumor specimens and plasma collected before surgery, using droplet digital polymerase chain reaction (ddPCR). ctDNA was defined as positive when the corresponding mutation between somatic and plasma was also detected in plasma cell-free DNA (cfDNA). Relationships of the presence of ctDNA with clinicopathological features were examined.

Results Somatic PIK3CA and/or KRAS mutations were found in 68 (34%) of 199 patients with endometrial cancer. Ten (14.7%) of 68 patients had similar mutations in cfDNA. ctDNA detected in pre-operative plasma was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.008), histology (p=0.028), and lymphovascular space invasion (p=0.002), and with shorter recurrence-free and overall survival (p=0.004 and p=0.010, respectively, by log-rank test).

Conclusion Tumor-related ctDNA detected in plasma before surgery was associated with poorer oncologic outcome on univariate analysis in patients with endometrial cancer harboring PIK3CA or KRAS mutations.

  • uterine cancer
  • endometrial neoplasms
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Footnotes

  • Contributors KH contributed to designing and supervising the study, editing the manuscript, and interpretation of the data. DS, TH, KT, and KW contributed to the analysis of blood and tissue samples. KH, SS, AO, AY, and KF contributed to data analysis and interpretation. DS performed analyses and drafted the manuscript. All authors contributed to writing the manuscript and approved the submitted and final versions.

  • Funding This study was partially supported by a grant from Hidaka Research Projects (29-D-1-08) at Saitama Medical University (DS) and a research grant from Eisai (KH).

  • Competing interests KH received a grant from Eisai

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Institutional Review Board of Saitama Medical University International Medical Center (#14-058). The study was performed in accordance with the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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