title: Neoadjuvant radiochemotherapy increases matrix metalloproteinase activity in healthy tissue in esophageal cancer patients.
abstract: BACKGROUND
  Neoadjuvant radiochemotherapy (RCT) is thought to result in a favorable oncological outcome in esophageal cancer patients. Unfortunately, it also implies that adjacent healthy tissue is preoperatively exposed to the potential damaging influence of RCT. Here, the impact of preoperative RCT on matrix metalloproteinase (MMP) expression in healthy esophageal tissue aligned with the tumor at the time of surgery is examined.
  
  
  METHODS
  23 patients participating in a clinical trial were randomized to either the control (n = 12) or the neoadjuvant RCT group (n = 11). In the latter group, surgery was performed 5 weeks after the last course of RCT. Full-thickness biopsies were taken from healthy esophageal tissue at the proximal border of the resection specimen and more distally next to the tumor. MMP-2 and MMP-9 activity in the samples was assessed by quantitative gelatin zymography and immunohistochemistry.
  
  
  RESULTS
  In the proximal segment, the activities of the MMP-9-dimer (135 kDa) and proMMP-9 (92 kDa) were significantly increased in the RCT group as compared with the control group: 28.5 versus 3.0 (p = 0.025) and 87.7 versus 13.0 (p = 0.015) arbitrary units for 135 kDa and 92 kDa, respectively. In the distal part, RCT resulted in a significant increase of proMMP-2 (72 kDa: 35.8 versus 17.8, p = 0.005) and proMMP-9 (81.2 versus 23.3, p = 0.03).
  
  
  CONCLUSIONS
  In esophageal cancer patients, neoadjuvant RCT results in increased MMP expression in healthy esophageal tissue as measured at the time of surgery. Since increased levels of MMPs are associated with severe postoperative complications including anastomotic leakage this finding necessitates further clinical research.
authors.affiliation: Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.
authors.forename: E A
authors.initials: EA
authors.lastname: Rieff
authors.forename: T
authors.initials: T
authors.lastname: Hendriks
authors.forename: H J T
authors.initials: HJ
authors.lastname: Rutten
authors.forename: G A P
authors.initials: GA
authors.lastname: Nieuwenhuijzen
authors.forename: M J E M
authors.initials: MJ
authors.lastname: Gosens
authors.forename: A J C
authors.initials: AJ
authors.lastname: van den Brule
authors.forename: S W
authors.initials: SW
authors.lastname: Nienhuijs
authors.forename: I H J T
authors.initials: IH
authors.lastname: de Hingh
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001706:Biopsy; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant
chemical_list: D016190:Carboplatin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D017239:Paclitaxel