Urinary mesothelin provides greater sensitivity for early stage ovarian cancer than serum mesothelin, urinary hCG free beta subunit and urinary hCG beta core fragment.
OBJECTIVE
Early detection of ovarian cancer should improve overall survival. Multiple serum markers have been evaluated as possible tests to detect early stage disease, but few urine markers have been studied. Mesothelin has been detected in serum from patients with ovarian cancer, but has not been previously reported in urine.


METHODS
Mesothelin was assayed in the serum and in the urine from 28 patients with early stage (I/II) invasive epithelial ovarian cancers, 111 with advanced stage (III/IV) invasive disease and 19 with tumors of low malignant potential. Marker values have been compared to those in healthy controls and 115 patients with benign pelvic masses. Thresholds were set to include 95% of mesothelin values for 127 sera and 89 urines from healthy women. Urine values were considered: (1) as assayed; (2) normalized using the ratio of serum to urine creatinine; and (3) normalized using the Cockroft-Gault formula for glomerular filtration rate (GFR). Urines were also assayed for human chorionic gonadotropin (hCG) free beta subunit and beta subunit core fragment and similarly normalized.


RESULTS
Optimal sensitivity for early stage disease was obtained when urine mesothelin was normalized using GFR. A greater fraction of patients with early stage disease was detected with the mesothelin urine assay (42%) than with the serum assay (12%). Similarly, 75% of patients with advanced ovarian cancer had elevated mesothelin in urine compared to 48% in serum. Serum and urine levels of mesothelin correlated for early (p=0.02) and late (p<0.001) disease. Urine mesothelin exhibited greater sensitivity for early stage ovarian cancer than did hCG free beta subunit or beta subunit core fragment and complementarity was not observed.


CONCLUSIONS
Urine mesothelin deserves further evaluation as a biomarker for detection of early stage ovarian cancer in combination with other urinary markers.
Badgwell
Donna
D
Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, Box 355, 1515 Holcombe Boulevard, Houston, TX 77030, and Program in Women's Oncology, Women's and Infants' Hospital, Providence, RI 02905, USA.
Lu
Zhen
Z
Cole
Laurence
L
Fritsche
Herbert
H
Atkinson
Edward N
EN
Somers
Elizabeth
E
Allard
Jeffrey
J
Moore
Richard G
RG
Lu
Karen H
KH
Bast
Robert C
RC
D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine*; D018394:CA-125 Antigen / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000652:urine*; D005260:Female; D058851:GPI-Linked Proteins; D005919:Glomerular Filtration Rate; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood / Q000652:urine*; D000090204:Mesothelin; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000473:pathology / Q000652:urine*; D010446:Peptide Fragments / Q000652:urine*; D012372:ROC Curve
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018997:Chorionic Gonadotropin, beta Subunit, Human; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; C063554:urinary gonadotropin fragment; D000090204:Mesothelin