Significant overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma using real-time quantitative reverse transcription polymerase chain reaction.
OBJECTIVE
Overexpression of urokinase-type plasminogen activator (uPA) has been shown to be strongly associated with an increased metastatic potential and poor prognosis in a variety of human malignancies. It was hypothesized that uPA would be overexpressed in highly metastatic pancreatic cancer. The aims of this study were to analyze uPA mRNA expression in pancreatic cancer and to correlate this to the expression of uPA protein and to the stage of the disease.


METHODS
Twenty-one pancreatic adenocarcinoma, six ampullary carcinoma and 10 benign mucinous cystadenoma samples, all with adjacent normal tissue, were collected. uPA mRNA was measured using real-time quantitative reverse transcription polymerase chain reaction. Localization of uPA within normal and pancreatic tumor sections was subsequently confirmed using immunohistochemistry.


RESULTS
The median and range of the ratios of uPA mRNA measures between tumor tissue and non-involved pancreatic tissue was 17.1 (1.4-653.6) for pancreatic adenocarcinoma (P < 0.001), 3.9 (0.7-7.7) for ampullary carcinoma (P = 0.055) and 1.9 (0.6-5.9) for mucinous cystadenoma tissue (P = 0.052). uPA low tumors were associated with an exuberant stromal reaction, whereas uPA high tumors showed little stromal response. Immunohistochemistry confirmed that uPA protein was more prevalent in pancreatic adenocarcinoma tissue than in normal tissue and that it was membrane-bound. uPA mRNA expression was significantly associated with poorly differentiated pancreatic cancers (P < 0.05) and positively associated with tumor stage.


CONCLUSIONS
These observations suggest that significant overexpression of uPA correlates closely to the rapid progression and invasiveness of pancreatic cancer and that uPA may provide a future therapeutic target for pancreatic cancer treatment.
Nielsen
Aiqun
A
The University of Sydney, Department of Surgery, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia.
Scarlett
Christopher J
CJ
Samra
Jaswinder S
JS
Gill
Anthony
A
Li
Yong
Y
Allen
Barry J
BJ
Smith
Ross C
RC
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D012333:RNA, Messenger; D014568:Urokinase-Type Plasminogen Activator