title: Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial.
abstract: We reported in a retrospective study that the presence of micrometastasis in lymph nodes, when assessed by carcinoembryonic antigen (CEA)-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer. The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial.
  
  
  
  From November 2001 to December 2005, a total of 419 colorectal cancer cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II colorectal cancer cases were enrolled. After RNA quality check, 304 colorectal cancer cases were analyzed for CEA mRNA in lymph nodes by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method.
  
  
  
  A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Postoperative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-fluorouracil derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for 1 year, whereas chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (high MMV, n = 95) was an independent poor prognostic factor for 5-year disease-free survival (DFS; P = 0.001) and 5-year overall survival (OS; P = 0.016).
  
  
  
  This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II colorectal cancer. Clin Cancer Res; 22(13); 3201-8. ©2016 AACR.
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan. Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan. hyamamoto@gesurg.med.osaka-u.ac.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Surgery, Suita Municipal Hospital, Osaka, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Murata
authors.affiliation: Department of Surgery, Hyogo Prefectural Nishinomiya Hospital, Hyogo, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Fukunaga
authors.affiliation: Department of Surgery, Nippon Telegraph and Telephone West Corporation Osaka Hospital, Osaka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ohnishi
authors.affiliation: Department of Surgery, Osaka Rosai Hospital, Osaka, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Noura
authors.affiliation: Department of Surgery, Nishinomiya Municipal Central Hospital, Hyogo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.affiliation: Department of Surgery, Kansai Rosai Hospital, Hyogo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Ohtsuka
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohue
authors.affiliation: Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Sekimoto
authors.affiliation: Department of Surgery, Nishinomiya Municipal Central Hospital, Hyogo, Japan.
authors.forename: Riichiro
authors.initials: R
authors.lastname: Nezu
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.affiliation: The Cancer Institute Hospital of JFCR, Tokyo, Japan.
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000032:analysis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061206:Neoplasm Micrometastasis / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D012333:RNA, Messenger; C017367:carmofur; D005472:Fluorouracil