International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2012
The prognostic and predictive value of combined HE4 and CA-125 in ovarian cancer patients.
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Steffensen Karina Dahl, Waldstrøm Marianne, Brandslund Ivan, Petzold Max, Jakobsen Anders
Аннотация
OBJECTIVE: A risk-of-ovarian-malignancy algorithm (ROMA) based on human epididymis protein 4 (HE4) and CA-125 has been reported to categorize women with a pelvic mass into high or low risk of ovarian malignancy. Originally, the ROMA score was developed for diagnostic purposes and the clinical application of HE4 for other purposes such as a predictor of survival or platinum resistance has not been extensively investigated. The objective of the present study was to evaluate the prognostic importance of prechemotherapy combined levels of HE4 and CA-125 and prediction of platinum resistance. Furthermore, we wanted to investigate the dynamics of the markers during treatment.
MATERIALS AND METHODS: Serum from 137 patients with newly diagnosed serous ovarian cancer was analyzed for CA-125 and HE4 using ELISAs in a training data set. Patients with high levels (upper third percentiles) of both HE4 and CA-125 were classified as high-risk patients. Data were validated in an independent data set of an additional 94 patients. HE4 and CA-125 were also analyzed at all cycles of subsequent chemotherapy.
RESULTS: The combined score of HE4 and CA-125 was highly predictive of both progression-free and overall survival in univariate as well as multivariate survival analysis. Values in the upper third percentiles (66th) were significantly associated with decreased progression-free and overall survival in both the training and in the validation set (P < 0.05 in all analyses).The positive predictive value in relation to platinum resistance was higher for the combination of markers than for the markers individually. The positive predictive values were 64.3% and 60.7% for combined CA-125/HE4 in the training and validation sets, respectively.
CONCLUSIONS: The combination of HE4 and CA-125 levels at baseline just before initiation of chemotherapy was significantly associated with decreased progression-free and overall survival and to some extent with platinum resistance.
MATERIALS AND METHODS: Serum from 137 patients with newly diagnosed serous ovarian cancer was analyzed for CA-125 and HE4 using ELISAs in a training data set. Patients with high levels (upper third percentiles) of both HE4 and CA-125 were classified as high-risk patients. Data were validated in an independent data set of an additional 94 patients. HE4 and CA-125 were also analyzed at all cycles of subsequent chemotherapy.
RESULTS: The combined score of HE4 and CA-125 was highly predictive of both progression-free and overall survival in univariate as well as multivariate survival analysis. Values in the upper third percentiles (66th) were significantly associated with decreased progression-free and overall survival in both the training and in the validation set (P < 0.05 in all analyses).The positive predictive value in relation to platinum resistance was higher for the combination of markers than for the markers individually. The positive predictive values were 64.3% and 60.7% for combined CA-125/HE4 in the training and validation sets, respectively.
CONCLUSIONS: The combination of HE4 and CA-125 levels at baseline just before initiation of chemotherapy was significantly associated with decreased progression-free and overall survival and to some extent with platinum resistance.
Предметные рубрики MeSH
AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCA-125 AntigenCarcinoma, Ovarian EpithelialDrug Resistance, NeoplasmFemaleHumansMembrane ProteinsMiddle AgedNeoplasms, Glandular and EpithelialOvarian NeoplasmsPredictive Value of TestsPrognosisProteinsSurvival AnalysisTreatment OutcomeWAP Four-Disulfide Core Domain Protein 2