Evaluation of HE4, CA125, Risk of Ovarian Malignancy Algorithm (ROMA) and Risk of Malignancy Index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass.
OBJECTIVE: Diagnostic factors are needed to improve the currently used serum CA125 and Risk of Malignancy Index (RMI) in differentiating ovarian cancer (OC) from other pelvic masses, thereby achieving precise and fast referral to a tertiary centre and correct selection for further diagnostics. The aim was to evaluate serum Human Epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) for these purposes.
METHODS: Serum from 1218 patients in the prospective ongoing pelvic mass study was collected prior to diagnosis. The HE4 and CA125 data were registered and evaluated separately and combined in ROMA and compared to RMI.
RESULTS: 809 benign tumors, 79 borderline ovarian tumors, 252 OC (64 early and 188 late stage), 9 non-epithelial ovarian tumors and 69 non-ovarian cancers were evaluated. Differentiating between OC and benign disease the specificity was 62.2 (CA125), 63.2 (HE4), 76.5 (ROMA) and 81.5 (RMI) at a set sensitivity of 94.4 which corresponds to RMI=200. The Areas Under the Curve (AUC) were 0.854 (CA125), 0.864 (HE4), 0,897 (ROMA) and 0.905 (RMI) for benign vs. early stage OC. For premenopausal benign vs. OC AUC were 0.925 (CA125), 0.905 (HE4), 0.909 (ROMA) and 0.945 (RMI).
CONCLUSION: HE4 and ROMA increase differentiating OC from other pelvic masses, even in early stage OC. ROMA might be valuable as a first line biomarker for selecting high risk patients for referral to a tertiary centre and further diagnostics. Further improvements of HE4 and ROMA in differentiating pelvic masses are still needed, especially regarding premenopausal women.Copyright © 2012. Published by Elsevier Inc.
Although bone pain in osteoporosis and skeletal metastasis is an expected consequence of fracture, there are other underlying causes responsible. Our study demonstrated that ovarian cancer G-protein-coupled receptor 1 detected extracellular protons in MG63 cells, and regulated osteoblast functions, such as prostaglandin E2 production, in response to acidic circumstances. In this work, we measured inositol phosphate production, intracellular Ca(2+) concentration, prostaglandin E2 production, and cyclic adenosine monophosphate accumulation in MG63 cells exposed to extracellular acidification. Extracellular acidity induced a transient increase in Ca(2+) concentration and inositol phosphate production. Acidification also induced prostaglandin E2 production, resulting in cyclic adenosine monophosphate accumulation. A small interfering RNA specific for the ovarian cancer G-protein-coupled receptor 1 markedly inhibited these proton-induced actions in MG63 cells. These results indicated that the involvement of ovarian cancer G-protein-coupled receptor 1 in acidic extracellular environment may be an underlying mechanism responsible for bone pain in osteoporosis or bone metastasis without clinically proved fractures.Copyright © 2012. Published by Elsevier Ltd.
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