Clinical impact of predicting CCND1 amplification using plasma DNA in superficial esophageal squamous cell carcinoma.
BACKGROUND
This study was designed to evaluate the clinical benefit of predicting the cyclin D1 (CCND1) status using cell-free plasma DNA in superficial esophageal squamous cell carcinoma (ESCC) patients.


METHODS
The ratio of the CCND1 (11q13) dosage to the DRD2 (11q22-23) dosage (C/D ratio) as the CCND1 copy number was evaluated. This study was divided into three steps: (1) demonstration of the feasibility, (2) evaluation of whether the plasma C/D ratio assay could monitor tumor dynamics, and (3) a validation study in 63 consecutive superficial ESCC (pTis-T1) patients and 40 healthy volunteers.


RESULTS
(1) The plasma C/D ratio was significantly higher (p = 0.0369) in superficial ESCC patients than in the controls in a preliminary test. (2) The high plasma C/D ratio appeared to reflect the tumor levels of the CCND1 status and was reduced in postoperative plasma samples (p = 0.1154) and samples following endoscopic resection (p = 0.0845). (3) Validation analysis revealed that the plasma C/D ratio was significantly higher in superficial ESCC patients than in controls (p < 0.0001). The frequency of recurrence was significantly higher (p = 0.0198), and recurrence-free survival was significantly shorter (p = 0.0075) in patients with a high plasma C/D ratio. Moreover, a high C/D ratio was shown to be an independent risk factor for recurrence on multivariate analysis [p = 0.0334; odds ratio 10.58 (range 1.203-93.23)].


CONCLUSIONS
The prediction of CCND1 amplification by plasma DNA may be a new complementary clinical biomarker for recurrence in patients with superficial ESCC.
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan, skomatsu@koto.kpu-m.ac.jp.
Shuhei
S
Komatsu
Daisuke
D
Ichikawa
Shoji
S
Hirajima
Hiroki
H
Takeshita
Atsushi
A
Shiozaki
Hitoshi
H
Fujiwara
Tsutomu
T
Kawaguchi
Mahito
M
Miyamae
Hirotaka
H
Konishi
Takeshi
T
Kubota
Kazuma
K
Okamoto
Nobuaki
N
Yagi
Eigo
E
Otsuji
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000378:metabolism*; D019938:Cyclin D1 / Q000097:blood* / Q000378:metabolism*; D004247:DNA / Q000097:blood*; D004938:Esophageal Neoplasms / Q000097:blood / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged
D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019938:Cyclin D1; D004247:DNA