title: Methylated DNA and high total DNA levels in the serum of patients with breast cancer following neoadjuvant chemotherapy are predictive of a poor prognosis.
abstract: In a previous study, we established a one-step methylation-specific polymerase chain reaction (OS-MSP) assay for the detection of methylated DNA (met-DNA) and total DNA levels in serum. For the present study, this OS-MSP assay was used for patients with breast cancer treated with neoadjuvant chemotherapy (NAC) in order to investigate the prognostic significance of met-DNA and total DNA levels. Following treatment with NAC and prior to surgery, serum samples obtained from 120 patients with stage II/III breast cancer were subjected to the OS-MSP assay for analysis of the glutathione S-transferase pi 1, Ras association (RalGDS/AF-6) domain family member 1 and retinoic acid receptor β2 genes. The detection of methylation in a minimum of one of these genes indicated a positive outcome of the assay. The total DNA content of the serum was also determined. Of the 120 stage II/III patients, seven (6%) were positive for met-DNA in serum and showed a significantly worse overall survival (OS) time compared with patients negative for met-DNA (n=113) (5-year OS, 43 vs. 85%; P=0.002). The patients with high total DNA levels in serum (n=40) also showed a significantly worse OS compared with those with low total DNA levels (n=80) (65 vs. 91%; P<0.001). The presence of met-DNA and high total DNA levels in the serum were found to be significant prognostic factors that are independent of a pathological complete response by multivariate analysis. Following NAC, met-DNA and high total DNA levels in the serum detected with the OS-MSP assay constitute novel prognostic factors for patients with breast cancer; this may be clinically useful for the prognosis prediction for patients who do not achieve a pathological complete response following NAC.
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Noriko
authors: N
authors: Fujita
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Naofumi
authors: N
authors: Kagara
authors: Central Research Laboratories, Sysmex Corporation, Kobe 651-2271, Japan.
authors: Noriaki
authors: N
authors: Yamamoto
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Kenzo
authors: K
authors: Shimazu
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Atsushi
authors: A
authors: Shimomura
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Masafumi
authors: M
authors: Shimoda
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Naomi
authors: N
authors: Maruyama
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Yasuto
authors: Y
authors: Naoi
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Koji
authors: K
authors: Morimoto
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Naofumi
authors: N
authors: Oda
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Seung Jin
authors: SJ
authors: Kim
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita-shi, Osaka 565-0871, Japan.
authors: Shinzaburo
authors: S
authors: Noguchi
keywords: DNA; breast cancer; methylation; neoadjuvant chemotherapy; prognosis; serum