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J Gynecol Oncol. 2019 May;30(3):e32. English. Original Article. https://doi.org/10.3802/jgo.2019.30.e32
Kim YM , Lee SW , Lee YJ , Lee HY , Lee JE , Choi EK .
Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. swhlee@amc.seoul.kr
Asan Institute for Life Sciences, Seoul, Korea.
DNA Link, Inc., Seoul, Korea.
Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Abstract

Objective

Somatic TP53 mutation (TP53mut ) is a characteristic finding in high-grade serous ovarian cancer (HGSOC). The aim of this study was to assess the clinical efficacy and utility of TP53mut circulating tumor DNA (ctDNA) monitoring as a biomarker for managing HGSOC.

Methods

TP53muts were evaluated in patients who received primary treatment for suspected ovarian cancer at Asan Medical Center. In patients diagnosed with HGSOC and with TP53mut , ctDNA, cancer antigen 125 (CA 125), and computed tomography were followed up according to the treatment course.

Results

Direct sequencing analysis of 103 tumor tissues from 61 HGSOC patients confirmed TP53muts in 41 patients (67.2%). All these patient-specific somatic mutations were detected in plasma cell-free DNA. The mean value of preoperative TP53 mutant allele count (TP53MAC) in stage III patients was 12.2 copies/µL and in stage IV patients was 45.3 copies/µL. TP53MAC was significantly reduced by treatment and there was no significant difference in the rate of decrease compared to CA 125 by the generalized linear mixed model. When patients were divided into a low TP53MAC group (< 0.2 copies/µL) and a high TP53MAC group (≥0.2 copies/µL) based on the TP53MAC value at 3 months after the end of chemotherapy, there was a significant difference in time to progression between the two groups (p=0.038).

Conclusion

TP53mut ctDNA shows potential as a tumor-specific biomarker for treatment response monitoring in HGSOC. TP53mut ctDNA levels at 3 months post treatment has a significant prognostic utility than that of CA 125.

Copyright © 2019. Korean Association of Medical Journal Editors.