Note: accompanying Editorial notes that this study was comprised of
postmenopausal women only
******************
JCO Early Release, published online ahead of print
Apr 5 2010
Journal of Clinical Oncology, 10.1200/JCO.2008.19.2484
Received August 3, 2008
Accepted January 5, 2010
Development of a Multimarker Assay for Early Detection of Ovarian Cancer (reference link for authors)
Purpose: Early detection of ovarian cancer has great promise
to improve clinical outcome.
Patients and Methods: Ninety-six
serum biomarkers were analyzed in sera from healthy women and
from patients with ovarian cancer, benign pelvic tumors, and
breast, colorectal, and lung cancers, using multiplex xMAP bead-based
immunoassays. A Metropolis algorithm with Monte Carlo simulation
(MMC) was used for analysis of the data.
Results: A training
set, including sera from 139 patients with early-stage ovarian
cancer, 149 patients with late-stage ovarian cancer, and 1,102
healthy women, was analyzed with MMC algorithm and cross validation
to identify an optimal biomarker panel discriminating early-stage
cancer from healthy controls. The four-biomarker panel providing
the highest diagnostic power of 86% sensitivity (SN) for early-stage
and 93% SN for late-stage ovarian cancer at 98% specificity
(SP) was comprised of CA-125, HE4, CEA, and VCAM-1. This model
was applied to an independent blinded validation set consisting
of sera from 44 patients with early-stage ovarian cancer, 124
patients with late-stage ovarian cancer, and 929 healthy women,
providing unbiased estimates of 86% SN for stage I and II and
95% SN for stage III and IV disease at 98% SP. This panel was
selective for ovarian cancer showing SN of 33% for benign pelvic
disease, SN of 6% for breast cancer, SN of 0% for colorectal
cancer, and SN of 36% for lung cancer.
Conclusion: A panel of
CA-125, HE4, CEA, and VCAM-1, after additional validation, could
serve as an initial stage in a screening strategy for epithelial
ovarian cancer.