title: Progressive loss of perivascular nerves adjacent to colorectal cancer.
abstract: OBJECTIVE
  The perivascular innervation of arterioles in colorectal cancer and adjacent submucosa was investigated.
  
  
  METHODS
  Neurotransmitter markers, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH), were studied and immunoreactivity was compared with that of control normal tissue.
  
  
  RESULTS
  There was absence of perivascular nerves within tumours and loss of perivascular innervation in the submucosa adjacent to the tumour. The pattern of loss varied for different transmitters. The loss was progressively greater with advancing tumour stage for NPY (controls 95%, Dukes' A 68%, Dukes>> B 13%, Dukes' C 6%) and VIP (50%, 23%, 20%, 17%). For TH there was extensive loss of innervation around tumours of all stages (69%, 5%, 7%, 0%). SP immunoreactive peri-arteriolar nerves were similar in control tissue (39%) and tissue adjacent to Dukes' A tumours (40%) but diminished to 19% and 0% in tissue adjacent to Dukes' B and C tumours, respectively. In none of the tissues was CGRP immunoreactivity above 4%. The mean distance over which there was reduced NPY immunoreactivity from the tumour edge was 2.43 mm for Dukes' A/B tumours compared with 7.20 mm for Dukes' C tumours; for VIP immunoreactivity this distance was 5.22 mm for Dukes' A/B tumours and 5.52 mm for Dukes' C tumours.
  
  
  CONCLUSIONS
  The progressive loss, both in terms of vascular nerve immunoreactivity and distance from the tumour edge with tumour grade, suggests that the tumour itself may influence neural integrity in perivascular plexuses, perhaps via the secretion of an inhibitory factor.
authors.affiliation: Department of Surgery, The Institute of Surgical Studies, Royal Free and University College Medical School, Charles Bell House, 67-73 Riding House Street, London, W1P 7LD, UK.
authors.forename: V L
authors.initials: VL
authors.lastname: Chamary
authors.forename: T
authors.initials: T
authors.lastname: Robson
authors.forename: M
authors.initials: M
authors.lastname: Loizidou
authors.forename: P B
authors.initials: PB
authors.lastname: Boulos
authors.forename: G
authors.initials: G
authors.lastname: Burnstock
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001160:Arterioles / Q000276:immunology / Q000294:innervation*; D014408:Biomarkers, Tumor / Q000276:immunology; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology; D003106:Colon / Q000098:blood supply* / Q000294:innervation; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009478:Neuropeptide Y / Q000276:immunology; D012007:Rectum / Q000098:blood supply* / Q000294:innervation; D013373:Substance P / Q000276:immunology; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; D009478:Neuropeptide Y; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D014446:Tyrosine 3-Monooxygenase; D015740:Calcitonin Gene-Related Peptide