Assessment of protein biomarkers for preoperative differential diagnosis between benign and malignant ovarian tumors

C. Landolfo, E. T.L. Achten, J. Ceusters, T. Baert, W. Froyman, R. Heremans, A. Vanderstichele, G. Thirion, A. Van Hoylandt, S. Claes, J. Oosterlynck, A. S. Van Rompuy, D. Schols, J. Billen, B. Van Calster, T. Bourne, T. Van Gorp, I. Vergote, D. Timmerman, A. Coosemans

Research output: Contribution to journalArticlepeer-review


Objective: To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. Methods: In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs. Results: CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80. Conclusions: The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.

Original languageEnglish
Pages (from-to)811-819
Number of pages9
JournalGynecologic Oncology
Issue number3
Publication statusPublished - Dec 2020
Externally publishedYes


  • Diagnosis
  • Immunosuppression
  • Ovarian cancer
  • Ovarian neoplasms
  • Tumor markers

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology


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