Matrix metalloproteinases in rectal mucosa, tumour and plasma: response after preoperative irradiation.
BACKGROUND
In rectal cancer treatment, preoperative radiotherapy has led to reduction of local recurrence, but it is associated with morbidity and increased risk for secondary tumours. Matrix metalloproteinases (MMPs) are associated with tumour progression through tissue remodeling. The aim of this study was to investigate tissue remodeling after preoperative radiotherapy and to explore possible correlations with clinical outcome.


METHODS
Ninety-one patients scheduled for rectal cancer surgery were included; 49% received preoperative radiotherapy three-field treatment, 5 x 5 Gy. Blood samples and biopsies from tumour and adjacent mucosa were taken during surgery. Biopsies and plasma were assayed with ELISA for MMP-1, MMP-2 and MMP-9. Clinical outcome was reviewed focusing on infections, perineal healing, fistula formation, anastomotic dehiscence, small bowel obstruction, local recurrence and distant metastases.


RESULTS
Compared to non-irradiated mucosa, MMP-2 (p < 0.0001), MMP-1 (p = 0.03) and MMP-9 (p = 0.04) were significantly higher in irradiated normal mucosa. Tumour tissue had higher levels of MMP-2 if irradiated (p < 0.0001). A correlation between MMP-2 levels and wound infection (p = 0.02) as well as fistula formation (p = 0.04) was found. MMP-1 in mucosa (p = 0.02) and tumour (p = 0.04) were higher in patients developing distant metastases. Plasma levels were not influenced by irradiation, but MMP-2 was higher in patients who were later developing distant metastases (p = 0.007).


CONCLUSIONS
Extracellular matrix remodeling after radiotherapy seems to be correlated to postoperative morbidity; MMP-2 is associated with both wound infections and fistula formation. High levels of MMP-1 in tumour and mucosa as well as MMP-2 in plasma may be correlated to risk of developing distant metastases.
Angenete
Eva
E
Department of Surgery, Sahlgrenska University Hospital/Ostra, Göteborg University, Gothenburg, Sweden. eva.angenete@vgregion.se
Langenskiöld
Marcus
M
Falk
Peter
P
Ivarsson
Marie-Louise
ML
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005402:Fistula / Q000201:enzymology; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D009092:Mucous Membrane / Q000201:enzymology*; D009367:Neoplasm Staging; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000097:blood / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy*; D012007:Rectum / Q000201:enzymology* / Q000473:pathology; D016896:Treatment Outcome
D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1