Circulating tumor DNA (ctDNA) is an important source for liquid biopsy to understand the molecular phenotype of a tumor non-invasively, and is also expected to be a diagnostic and prognostic marker in cancer patients. Our aim is to clarify the clinical features of ctDNA in patients with ovarian cancer.
We screened 304 patients with ovarian tumors for somatic PIK3CA or KRAS mutations by a PCR-based method. A total of 108 patients with ovarian tumors were found to have somatic PIK3CA and/or KRAS mutations. One hundred and four out of 108 patients were considered to be evaluable for ctDNA. Cell-free DNA from the plasma of patients before surgery was investigated using droplet digital PCR for PIK3CA or KRAS mutations. We defined ctDNA detection to be positive when the corresponding mutations were detected in the plasma cell-free DNA.
In 104 patients, 75, 25, and 4 patients had malignant, borderline, and benign ovarian tumors, respectively. The detection rates for ctDNA were 32% (24/75), 16% (4/25), and 0% (0/4) in patients with malignant, borderline, and benign ovarian tumors, respectively. PIK3CA and KRAS mutations in the plasma cell-free DNA were detected in 33.3% (11/33) and 30.2% (13/43) of patients with malignant ovarian tumors, respectively. We investigated the relationship between ctDNA detection and clinico-pathological features in 73 epithelial ovarian cancer (EOC) patients. The detection rate of ctDNA was associated with advanced stage (p = 0.019) and positive peritoneal cytology (p = 0.011), but not with the histologic subtype or residual tumor status. In addition, we examined the potential association of ctDNA with patient survival. In univariate analysis, ctDNA detection was associated with shorter progression-free survival in EOC patients (p
ctDNA was detected in approximate 30% of EOC patients in this study regardless of histologic types or the genes examined. The presence of ctDNA in the blood was an independent prognostic factor for recurrence, which suggests potential tumor spread.
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Department of Gynecologic Oncology, Saitama Medical University International Medical Center
Eisai Co., Ltd.
K. Hasegawa: Research grant from Eisai Co., Ltd. All other authors have declared no conflicts of interest.