title: Clinical significance of perineural invasion in stages II and III colorectal cancer.
abstract: OBJECTIVE
  This study aimed to determine the prognostic value of perineural invasion (PNI) in patients with colorectal cancer (CRC), particularly patients with TNM stage II and stage III.
  
  
  METHODS
  A total of 159 CRC patients who had undergone radical resection were retrospectively analyzed. Histopathological evaluation of tissue samples was conducted on hematoxylin and eosin-stained sections. PNI was considered positive when cancer cells were observed inside the nerve sheath, or when at least 33% of the nerve periphery was surrounded by cancer cells. A 3-tier grading system (PNI0, PNI1, PNI2) based on the depth of PNI was used to assess the localization of PNI in the bowel. PNI and other prognostic factors were evaluated by survival analysis.
  
  
  RESULTS
  PNI status in CRC significantly affected postoperative overall survival (P<0.001). The five-year survival rates for PNI-negative and PNI-positive patients were 77% and 32%, respectively. PNI was closely correlated with tumor gross type, tumor grade, depth of invasion, lymph node metastasis, clinical stage, vessel invasion, tumor budding grade, and tumor growth pattern. Multivariate analysis revealed that PNI was an independent prognostic factor (HR=2.223, P=0.003). The survival of PNI-positive patients was significantly poorer than that of PNI-negative patients in stages II and III (P=0.003 and P=0.008, respectively). The overall survival of colorectal patients was in the descending order of PNI-negative at stage II, PNI-positive at stage II/PNI-negative at stage III, and PNI-positive at stage III (P<0.001). When the PNI status and T stage were considered together, overall survival curves of the PNI2 patients were significantly worse than those of PNI1 patients in pT4 stage (P=0.019).
  
  
  CONCLUSIONS
  PNI is a poor independent prognostic factor for CRC. It could complement classic TNM staging classification in stratifying CRC patients in stages II and III. Assessment of the site-specific distribution of PNI may further enhance the impact of PNI contribution to the prognosis of CRC.
authors.affiliation: Institute for Cancer Research, Health Science Center of Xi'an Jiaotong University, Xi'an, China; Department of Pathology, Xi'an Medical University, Xi'an, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Gong
authors.affiliation: Institute for Cancer Research, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Pathology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Institute for Cancer Research, Health Science Center of Xi'an Jiaotong University, Xi'an, China. Electronic address: wangyili@mail.xjtu.edu.cn.
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging / Q000379:methods*; D010525:Peripheral Nerves / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
keywords: Colorectal cancer; Perineural invasion; Prognosis