title: Prognostic significance of p21 expression in patients with esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Although p21 is an important component that regulates cell-cycle progression, no consensus has been reached about its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). In the present study, we investigated its prognostic significance and correlation with cyclin-D1 (CCND1) expression in ESCC.
  
  
  METHODS
  The p21 labeling index (LI) was calculated by immunohistochemistry for 69 primary tumor samples obtained from patients with ESCC who had undergone curative esophagectomy, and correlations between p21 LI and various clinicopathological features, prognosis, and CCND1 LI were studied.
  
  
  RESULTS
  The p21 LI of these tumors ranged from 2.0% to 57.0% (median=28.4%, mean±SD=27.3% ± 13.0). p21 LI was positively correlated with CCND1 LI. When patients were divided into two groups using a p21 LI cut-off value of 30%, the 5-year survival rate of patients with p21 LI of ≥ 30% was 80.0%, which was significantly higher than that of patients with p21 LI of <30% (55.5%). Furthermore, when patients were divided into four groups according to p21 and CCND1 expression, the 5-year survival rate of patients with p21 LI of <30% and CCND1 LI of ≥ 45% was the lowest (44.4%). Multivariate analysis demonstrated that venous invasion, lymphatic invasion, and p21 LI were independent prognostic factors.
  
  
  CONCLUSIONS
  Our results indicate that p21 LI is correlated with CCND1 LI and can be used as an independent prognostic factor for patients with ESCC following selection of a suitable cut-off value.
authors.affiliation: Assistant Professor, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. shiozaki@koto.kpu-m.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakashima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Konishi
authors.forename: Shuhei
authors.initials: S
authors.lastname: Komatsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kubota
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iitaka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Nako
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takemoto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kishimoto
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019938:Cyclin D1
keywords: esophageal squamous cell carcinoma; p21; prognostic factor