Influence of ovarian cancer risk status on the diagnostic performance of the serum biomarkers mesothelin, HE4, and CA125.
OBJECTIVE
To evaluate the effect of ovarian cancer risk on the performance of the serum biomarkers mesothelin, human epididymis protein 4 (HE4), and CA125.


METHODS
We measured mesothelin, HE4, and CA125 levels from women with invasive ovarian cancer (n = 143), benign gynecologic conditions (n = 124), and controls (n = 344). Demographic, epidemiologic, reproductive, medical, and family history data were collected using a standardized questionnaire. Pedigree and BRCA 1/2 test results were used to stratify women into average and high-risk groups. The diagnostic accuracy of each biomarker was characterized using receiver operating characteristic curve methods.


RESULTS
Baseline characteristics did not vary by risk or case status. The distribution of stage and histology was similar in average and high-risk women. All three markers discriminated ovarian cancer cases from risk-matched healthy and benign controls. Marker performance did not vary by risk status. The sensitivity at 95% specificity for discriminating cases from risk-matched healthy control women in the average and high-risk groups, respectively, was 53.9% and 39.0% for mesothelin, 80.4% and 87.8% for HE4, and 79.4% and 82.9% for CA125. The performance of the markers was not as robust when cases were compared with benign controls. Area under the curve values for cases versus healthy and benign controls did not vary by risk status.


CONCLUSIONS
The ability of serum mesothelin, HE4, and CA 125 levels to discriminate ovarian cancer cases from healthy and benign controls is not influenced by risk status. Our findings support the pursuit of additional studies evaluating the early detection potential of these markers in high-risk populations.
University of Washington, Seattle, WA 98195, USA. cshah@u.washington.edu
Chirag A
CA
Shah
Kimberly A
KA
Lowe
Pamela
P
Paley
Erin
E
Wallace
Garnet L
GL
Anderson
Martin W
MW
McIntosh
M Robyn
MR
Andersen
Nathalie
N
Scholler
Lindsay A
LA
Bergan
Jason D
JD
Thorpe
Nicole
N
Urban
Charles W
CW
Drescher
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D030501:Epididymal Secretory Proteins / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood*; D000090204:Mesothelin; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D023083:beta-Defensins
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C426184:DEFB126 protein, human; D030501:Epididymal Secretory Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D023083:beta-Defensins; D000090204:Mesothelin