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World Journal of Surgery

Published in:

01-03-2007

High Expression of Plasminogen Activator Inhibitor-2 (PAI-2) is a Predictor of Improved Survival in Patients with Pancreatic Adenocarcinoma

Authors: Ross Smith, AiQun Xue, Anthony Gill, Christopher Scarlett, Alexander Saxby, Adele Clarkson, Thomas Hugh

Published in: World Journal of Surgery | Issue 3/2007

Abstract

Objective

Recent findings suggest that the urokinase-type plasminogen activator (uPA), its receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and -2 (PAI-2) play key roles in cancer invasion.

Summary Background Data

The prognostic value of components of this system is well established in breast cancer. However, little is known of its involvement in pancreatic cancer (PC).

Methods

Quantitative real-time polymerase chain reaction (Q-RT-PCR) was used on tissue-banked specimens and immunohistochemistry (IHC) on paraffin specimens was used to measure expression of uPA, uPAR, PAI-1, and PAI-2 proteins in 46 PC and 12 cystadenoma specimens. Results were related to survival using Cox’s proportional hazards testing.

Results

Increased expression of uPA, uPAR, and PAI-1 in PC tissue were independently associated with a higher Union Internationale Contre le Cancer [International Union Against Cancer (UICC)] tumor stage (P < 0.001) and were intercorrelated (P < 0.001). Overexpression of uPAR indicated reduced survival (P = 0.03). Conversely, PAI-2 messenger ribonucleic acid (mRNA) overexpression, which occurred in 21 of 46 tumors, negatively correlated with tumor size (P = 0.008) and survival (P < 0.007) but not with uPA, uPAR, or tumor stage. There was good agreement between PAI-2 mRNA value and IHC score (P < 0.001). Using Cox’s stepwise analysis, PAI-2 mRNA value (HR = 0.24; P = 0.001) and UICC tumor stage (HR = 2.014; P = 0.001) independently predicted survival. An IHC score for PAI-2 of 3+ or 4+ also independently predicted improved survival (HR = 2.72; P = 0.025).

Conclusions

The uPA/uPAR/PAI-1 system is activated in advanced pancreatic cancer and may account for the tumor’s aggressive behavior, whereas PAI-2 expression appears to be independent of uPA/uPAR/PAI-1 and is associated with improved prognosis. Because of its intercorrelation with mRNA expression, PAI-2 IHC may be used as an indicator of survival.

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Title: High Expression of Plasminogen Activator Inhibitor-2 (PAI-2) is a Predictor of Improved Survival in Patients with Pancreatic Adenocarcinoma
Authors: Ross Smith
AiQun Xue
Anthony Gill
Christopher Scarlett
Alexander Saxby
Adele Clarkson
Thomas Hugh
Publication date: 01-03-2007
Publisher: Springer-Verlag
Published in: World Journal of Surgery / Issue 3/2007
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-006-0289-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

High Expression of Plasminogen Activator Inhibitor-2 (PAI-2) is a Predictor of Improved Survival in Patients with Pancreatic Adenocarcinoma

Abstract

Objective

Summary Background Data

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Summary Background Data

Methods

Results

Conclusions

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