uPA and PAI-1 in rectal cancer--relationship to radiotherapy and clinical outcome.
BACKGROUND
It is well known that the fibrinolytic system is of importance in inflammation, wound healing, and fibrosis development. However, it is also important in the process of tumor invasion and metastasis. We have investigated protein levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in rectal cancer and effects of radiotherapy, links to clinical outcome, and potential use as prognostic factors.


METHODS
Ninety-one patients with rectal cancer were studied. Blood samples and biopsies were taken during surgery and assayed with enzyme-linked immunosorbent assay for uPA and PAI-1, and patients were followed prospectively (0-96 mo).


RESULTS
Higher levels of uPA (P < 0.0001) and PAI-1 (P < 0.0001) were found in tumor compared with mucosa. Mucosa exposed to radiotherapy had higher levels of uPA (P < 0.0001) and of PAI-1 (P < 0.0001). Irradiated tumor tissue had higher levels of PAI-1 (P < 0.001). PAI-1 in tumor was correlated with T stage (P < 0.001) and N stage (P < 0.01). PAI-1 in plasma was higher in patients with synchronous distant metastases (P < 0.001). Cox regression was used to identify high levels of PAI-1 in tumor as an independent factor related to short disease-free survival (P < 0.01) and the ratio of uPA/PAI-1 to development of metastases (P < 0.01).


CONCLUSIONS
There is a relationship between PAI-1 in plasma and rectal cancer metastases. PAI-1 in tumor tissue is correlated to histopathological data and to outcome of rectal cancer. If these findings can be confirmed in larger trials, there will be a possibility to use PAI-1 as a prognostic factor.
Angenete
Eva
E
Department of Surgery, Sahlgrenska University Hospital/Ostra, Göteborg University, Gothenburg, Sweden. eva.angenete@vgregion.se
Langenskiöld
Marcus
M
Palmgren
Ingrid
I
Falk
Peter
P
Oresland
Tom
T
Ivarsson
Marie-Louise
ML
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy; D012007:Rectum / Q000737:chemistry / Q000528:radiation effects; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000097:blood / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator