title: Histogenesis and prognostic value of myenteric spread in colorectal cancer: a Japanese multi-institutional study.
abstract: BACKGROUND
  The histogenesis of the pattern of cancer spread along Auerbach's plexus (myenteric spread: MS) remains unclear and its prognostic value in colorectal cancer (CRC) has not been thoroughly investigated.
  
  
  METHODS
  Pathology slides of 2845 pT2/pT3/pT4 CRCs stained with hematoxylin-eosin (H&E) were reviewed at 10 institutions. MS was classified into 2 groups depending on whether it was accompanied by the finding of perineural invasion (PN) within the lesion. In addition, immunohistochemical staining (D2-40, S100, CD56, synaptophysin) was performed for serially sectioned specimens from 50 CRCs diagnosed as having PN-negative MS.
  
  
  RESULTS
  MS was observed in 504 patients (17.7 %); 360 patients were classified as having PN-positive MS and 144 as having PN-negative MS. The 5-year disease-free survival rate of patients with MS was lower than that of patients without MS (63.3 vs 82.7 %, P < 0.0001); however, there was no significant difference in survival outcome according to the presence or absence of intralesion PN in MS. Multivariate analysis showed that the prognostic impact of MS was independent of conventional prognosticators including T and N stages, vascular invasion and extramural PN. In all the tumors having PN-negative MS, remnants of neural tissue were identified within or around cancer nests located at the leading edge of MS.
  
  
  CONCLUSIONS
  MS is an important prognostic factor for CRC. This feature is the result of cancer development with replacement of Auerbach's plexus and can be classified as intramural PN. The clinical significance of "Pn1" in the UICC/AJCC TNM classification could be enhanced by individual assessment both intramurally and extramurally.
authors.affiliation: Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan, ueno@ndmc.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shimazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okuno
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yamada
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Sato
authors.forename: Takaya
authors.initials: T
authors.lastname: Kusumi
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kushima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikegami
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.forename: Akihiko
authors.initials: A
authors.lastname: Murata
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Akagi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009197:Myenteric Plexus / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult