title: The prognostic effect of perineural invasion in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Perineural invasion (PNI) is correlated with adverse survival in several malignancies, but its significance in esophageal squamous cell carcinoma (ESCC) remains to be clearly defined. The objective of this study was to determine the association between PNI status and clinical outcomes.
  
  
  METHODS
  We retrospectively evaluated the PNI of 433 patients with ESCC treated with surgery between 2000 and 2007 at a single academic center. The resulting data were analyzed using Spearman's rank correlation, the Kaplan-Meier method, Cox proportional hazards regression modeling and Harrell's concordance index (C-index).
  
  
  RESULTS
  PNI was identified in 209 of the 433 (47.7%) cases of ESCC. The correlation analysis demonstrated that PNI in ESCC was significantly correlated with tumor differentiation, infiltration depth, pN classification and stage (P < 0.05). The five-year overall survival rate was 0.570 for PNI-negative tumors versus 0.326 for PNI-positive tumors. Patients with PNI-negative tumors exhibited a 1.7-fold increase in five-year recurrence-free survival compared with patients with PNI-positive tumors (0.531 v 0.305, respectively; P < 0.0001). In the subset of patients with node-negative disease, PNI was evaluated as a prognostic predictor as well (P < 0.05). In the multivariate analysis, PNI was an independent prognostic factor for overall survival (P = 0.027). The C-index estimate for the combined model (PNI, gender and pN status) was a significant improvement on the C-index estimate of the clinicopathologic model alone (0.739 v 0.706, respectively).
  
  
  CONCLUSIONS
  PNI can function as an independent prognostic factor of outcomes in ESCC patients, and the PNI status in primary ESCC specimens should be considered for therapy stratification.
authors.forename: Jie-Wei
authors.initials: JW
authors.lastname: Chen
authors.forename: Jing-Dun
authors.initials: JD
authors.lastname: Xie
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Ling
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Yan
authors.forename: Shao-Yan
authors.initials: SY
authors.lastname: Xi
authors.forename: Rong-Zhen
authors.initials: RZ
authors.lastname: Luo
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yun
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. caimuyan@hotmail.com.
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D010525:Peripheral Nerves / Q000473:pathology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors