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Plasma Levels of Trefoil Factors are Increased in Patients with Advanced Prostate Cancer

Authors' Affiliations: Departments of ¹ Clinical Biochemistry and ² Urology, Aarhus University Hospital, Skejby Hospital, Aarhus, ³ Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus Hospital, Aarhus, and ⁴ Department of Medical Anatomy B, University of Copenhagen, Copenhagen, Denmark

Requests for reprints: Else Marie Vestergaard, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby Hospital, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark. Phone: 45-89495102; E-mail: else.marie.vestergaard{at}dadlnet.dk.

Purpose: Through cDNA array analyses and immunohistochemistry on tissue microarrays, trefoil factor 3 (TFF3) was recently shown to be overexpressed in prostate cancer. The purpose of this study was to test the feasibility of using the levels of trefoil factors as a plasma marker for prostate cancer.

Experimental Design: In 79 patients with prostate cancer, 23 patients with benign prostatic hyperplasia, and 44 healthy individuals plasma TFF1, TFF2, and TFF3 were determined with ELISAs and compared with clinical stage and prostate-specific antigen (PSA) values. Plasma levels of TFF were compared with the immunohistochemical expression of TFF and chromogranin A in 30 prostate cancer tissue samples.

Results: Patients with advanced prostate cancer had significantly higher plasma concentrations of TFF1, TFF2, and TFF3 (P < 0.01) compared with patients with localized disease. Using a cutoff of 200 pmol/L, the sensitivity and specificity of plasma TFF3 in differentiating between patients with localized and advanced disease was 74% (59-85%) and 81% (66-91%). Plasma levels of TFF3 were highest in patients with bone metastases (P = 0.008). Patients with serum PSA >10 µg/L had significantly higher plasma TFF3 values than patients with serum PSA <10 µg/L (P = 0.03) and TFF3 levels were higher in patients with Gleason sums of 7 (P = 0.02). Expression of TFF1 and TFF3 determined by immunohistochemistry was increased in patients with prostate cancer but did not correlate with plasma trefoil factor values.

Conclusions: Plasma levels of trefoil factors are increased in patients with advanced prostate cancer. Prospective studies are needed to confirm the predictive utility of trefoil factors in prostate cancer.