title: Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes.
abstract: BACKGROUND
  Colorectal cancer staging criteria do not rely on examination of neuronal tissue. The authors previously demonstrated that perineural invasion is an independent prognostic factor of outcomes in colorectal cancer. For the current study, they hypothesized that neurogenesis occurs in colorectal cancer and portends an aggressive tumor phenotype.
  
  
  METHODS
  In total, samples from 236 patients with colorectal cancer were used to create a tissue array and database. Tissue array slides were immunostained for protein gene product 9.5 (PGP9.5) to identify nerve tissue. The correlation between markers of neurogenesis and oncologic outcomes was determined. The effect of colorectal cancer cells on stimulating neurogenesis in vitro was evaluated using a dorsal root ganglia coculture model.
  
  
  RESULTS
  Patients whose tumors exhibited high degrees of neurogenesis had 50% reductions in 5-year overall survival and disease-free survival compared with patients whose tumors contained no detectable neurogenesis (P = .002 and P = .006, respectively). Patients with stage II disease and high degrees of neurogenesis had greater reductions in 5-year overall survival and disease-free survival compared with lymph node-negative patients with no neurogenesis (P = .002 and P = .008, respectively). Patients with stage II disease and high degrees of neurogenesis had lower 5-year overall survival and disease-free survival compared with patients who had stage III disease with no neurogenesis (P = .01 and P = .008, respectively). Colorectal cancer cells stimulated neurogenesis and exhibited evidence of neuroepithelial interactions between nerves and tumor cells in vitro.
  
  
  CONCLUSIONS
  Neurogenesis in colorectal cancer appeared to play a critical role in colorectal cancer progression. Furthermore, the current results indicated that neurogenesis functions as an independent predictor of outcomes and may play a role in therapy stratification for patients with lymph node-negative disease.
authors.affiliation: Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA. dalbo@bcm.edu
authors.forename: Daniel
authors.initials: D
authors.lastname: Albo
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Akay
authors.forename: Christy L
authors.initials: CL
authors.lastname: Marshall
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Wilks
authors.forename: Gordana
authors.initials: G
authors.lastname: Verstovsek
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Neeti
authors.initials: N
authors.lastname: Agarwal
authors.forename: David H
authors.initials: DH
authors.lastname: Berger
authors.forename: Gustavo E
authors.initials: GE
authors.lastname: Ayala
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D055495:Neurogenesis; D011379:Prognosis; D046888:Tissue Array Analysis