Ulla-Maija Haltia1, Marianne Hallamaa2, Johanna Tapper3, Johanna Hynninen2, Henrik Alfthan4, Bhanu Kalra5, Olli Ritvos6, Markku Heikinheimo7, Leila Unkila-Kallio3, Antti Perheentupa8, Anniina Färkkilä9. 1. Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland. 2. Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, 20520 Turku, Finland. 3. Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland. 4. Clinical Chemistry, University of Helsinki and HUSLAB, Finland. 5. AnshLabs, Webster, TX, USA. 6. Physiology, Faculty of Medicine, University of Helsinki, Finland. 7. Children's Hospital, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland; Department of Pediatrics, St. Louis Children´s Hospital, Washington University School of Medicine, St. Louis, MO 63110, USA. 8. Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, 20520 Turku, Finland; Department of Physiology, Institute of Biomedicine, University of Turku, 20014 Turku, Finland. 9. Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland. Electronic address: Anniina.farkkila@helsinki.fi.
Abstract
OBJECTIVE: Evaluation of circulating tumor markers in ovarian cancer is crucial for optimal patient care. The goal of this study was to verify the most accurate circulating tumor markers for the diagnosis and follow-up of adult-type granulosa cell tumors (AGCTs). METHODS: The levels of circulating human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125), together with AGCT markers inhibin B and anti-Müllerian hormone (AMH), were measured in 135 samples from AGCT patients, 37 epithelial ovarian carcinoma (EOC) patients, and 40 endometrioma (ENDO) patients. The levels were plotted with receiver operating characteristic (ROC) graphs, and the area under the curves (AUC) of the different markers were calculated and compared. RESULTS: HE4 levels were significantly lower in AGCTs than in EOCs (p<0.0001). CA125 levels were above 35IU/l in 25% of AGCT patients and 47.5% of ENDO patients, whereas inhibin B and AMH levels were elevated only in patients with AGCTs. In the AUC comparison analyses, inhibin B alone was sufficient to differentiate AGCT from EOC. In differentiating AGCT from ENDO, inhibin B and AMH performed similarly, and the combination of inhibin B and AMH increased the accuracy compared to either marker alone (sensitivity, 100%; specificity, 93%). Among AGCT patients, inhibin B was the best marker for detecting the presence of AGCT. CONCLUSIONS: HE4 and CA125 levels were low in AGCTs, and inhibin B was the most accurate circulating biomarker in distinguishing AGCTs from EOCs and from ENDOs. Inhibin B was also the best single marker for AGCT follow-up.
OBJECTIVE: Evaluation of circulating tumor markers in ovarian cancer is crucial for optimal patient care. The goal of this study was to verify the most accurate circulating tumor markers for the diagnosis and follow-up of adult-type granulosa cell tumors (AGCTs). METHODS: The levels of circulating humanepididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125), together with AGCT markers inhibin B and anti-Müllerian hormone (AMH), were measured in 135 samples from AGCT patients, 37 epithelial ovarian carcinoma (EOC) patients, and 40 endometrioma (ENDO) patients. The levels were plotted with receiver operating characteristic (ROC) graphs, and the area under the curves (AUC) of the different markers were calculated and compared. RESULTS:HE4 levels were significantly lower in AGCTs than in EOCs (p<0.0001). CA125 levels were above 35IU/l in 25% of AGCT patients and 47.5% of ENDO patients, whereas inhibin B and AMH levels were elevated only in patients with AGCTs. In the AUC comparison analyses, inhibin B alone was sufficient to differentiate AGCT from EOC. In differentiating AGCT from ENDO, inhibin B and AMH performed similarly, and the combination of inhibin B and AMH increased the accuracy compared to either marker alone (sensitivity, 100%; specificity, 93%). Among AGCT patients, inhibin B was the best marker for detecting the presence of AGCT. CONCLUSIONS:HE4 and CA125 levels were low in AGCTs, and inhibin B was the most accurate circulating biomarker in distinguishing AGCTs from EOCs and from ENDOs. Inhibin B was also the best single marker for AGCT follow-up.
Authors: Renée T Fortner; Helena Schock; Seungyoun Jung; Naomi E Allen; Alan A Arslan; Louise A Brinton; Brian L Egleston; Roni T Falk; Marc J Gunter; Kathy J Helzlsouer; Annika Idahl; Theron S Johnson; Rudolf Kaaks; Vittorio Krogh; Eva Lundin; Melissa A Merritt; Carmen Navarro; N Charlotte Onland-Moret; Domenico Palli; Xiao-Ou Shu; Patrick M Sluss; Paul N Staats; Antonia Trichopoulou; Elisabete Weiderpass; Anne Zeleniuch-Jacquotte; Wei Zheng; Joanne F Dorgan Journal: Br J Cancer Date: 2017-09-05 Impact factor: 7.640