Highly Accurate Detection of Ovarian Cancer Using CA125 but Limited Improvement With Serum Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Profiling

Tiss, Ali PhD*; Timms, John F. PhD†; Smith, Celia BSc*; Devetyarov, Dmitry PhD‡; Gentry-Maharaj, Aleksandra PhD†; Camuzeaux, Stephane BSc†; Burford, Brian PhD‡; Nouretdinov, Ilia PhD‡; Ford, Jeremy BSc†; Luo, Zhiyuan PhD‡; Jacobs, Ian MD†; Menon, Usha MD†; Gammerman, Alex PhD‡; Cramer, Rainer PhD*

International Journal of Gynecological Cancer: December 2010 - Volume 20 - Issue 9 - pp 1518-1524
doi: 10.1111/IGC.0b013e3181fc1990
Ovarian Cancer

Objectives: Our objective was to test the performance of CA125 in classifying serum samples from a cohort of malignant and benign ovarian cancers and age-matched healthy controls and to assess whether combining information from matrix-assisted laser desorption/ionization (MALDI) time-of-flight profiling could improve diagnostic performance.

Materials and Methods: Serum samples from women with ovarian neoplasms and healthy volunteers were subjected to CA125 assay and MALDI time-of-flight mass spectrometry (MS) profiling. Models were built from training data sets using discriminatory MALDI MS peaks in combination with CA125 values and tested their ability to classify blinded test samples. These were compared with models using CA125 threshold levels from 193 patients with ovarian cancer, 290 with benign neoplasm, and 2236 postmenopausal healthy controls.

Results: Using a CA125 cutoff of 30 U/mL, an overall sensitivity of 94.8% (96.6% specificity) was obtained when comparing malignancies versus healthy postmenopausal controls, whereas a cutoff of 65 U/mL provided a sensitivity of 83.9% (99.6% specificity). High classification accuracies were obtained for early-stage cancers (93.5% sensitivity). Reasons for high accuracies include recruitment bias, restriction to postmenopausal women, and inclusion of only primary invasive epithelial ovarian cancer cases. The combination of MS profiling information with CA125 did not significantly improve the specificity/accuracy compared with classifications on the basis of CA125 alone.

Conclusions: We report unexpectedly good performance of serum CA125 using threshold classification in discriminating healthy controls and women with benign masses from those with invasive ovarian cancer. This highlights the dependence of diagnostic tests on the characteristics of the study population and the crucial need for authors to provide sufficient relevant details to allow comparison. Our study also shows that MS profiling information adds little to diagnostic accuracy. This finding is in contrast with other reports and shows the limitations of serum MS profiling for biomarker discovery and as a diagnostic tool.

*BioCentre and Department of Chemistry, University of Reading, United Kingdom; †EGA Institute for Women's Health, University College London, United Kingdom; and ‡Computer Learning Research Centre, Royal Holloway, University of London, United Kingdom.

Received April 16, 2010.

Accepted for publication September 13, 2010.

Address correspondence and reprint requests to Rainer Cramer, PhD, The BioCentre and Department of Chemistry, University of Reading, Harborne Building, Whiteknights, PO Box 221, Reading, RG6 6AS, United Kingdom. E-mail: r.k.cramer@rdg.ac.uk.

Ali Tiss and John F. Timms contributed equally to this work.

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Copyright © 2010 by IGCS and ESGO