ABSTRACT
BACKGROUND: Previous results obtained from serum samples of late-stage, high-grade serous ovarian carcinoma patients showed large alterations in lipid metabolism. To validate and extend the results, we studied lipidomic changes in early-stage ovarian tumours. In addition to serous ovarian cancer, we investigated whether these changes occur in mucinous and endometrioid histological subtypes as well. METHODS: Altogether, 354 serum or plasma samples were collected from three centres, one from Germany and two from Finland. We performed lipidomic analysis of samples from patients with malignant (N = 138) or borderline (N = 25) ovarian tumours, and 191 controls with benign pathology. These results were compared to previously published data. RESULTS: We found 39 lipids that showed consistent alteration both in early- and late-stage ovarian cancer patients as well as in pre- and postmenopausal women. Most of these changes were already significant at an early stage and progressed with increasing stage. Furthermore, 23 lipids showed similar alterations in all investigated histological subtypes. CONCLUSIONS: Changes in lipid metabolism due to ovarian cancer occur in early-stage disease but intensify with increasing stage. These changes occur also in other histological subtypes besides high-grade serous carcinoma. Understanding lipid metabolism in ovarian cancer may lead to new therapeutic and diagnostic alternatives.
Subject(s)
Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Mucinous/pathology , Carcinoma, Endometrioid/pathology , Cystadenocarcinoma, Serous/pathology , Lipid Metabolism , Ovarian Neoplasms/pathology , Adenocarcinoma, Clear Cell/metabolism , Adenocarcinoma, Mucinous/metabolism , Adult , Aged , Biomarkers, Tumor/blood , Carcinoma, Endometrioid/metabolism , Chromatography, Liquid , Cystadenocarcinoma, Serous/metabolism , Female , Finland , Germany , Humans , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/metabolism , Postmenopause/blood , Premenopause/blood , Tandem Mass SpectrometryABSTRACT
OBJECTIVES: Elevated concentrations of polyamines have been found in urine of patients with malignant tumors, including ovarian cancer. Previous research has suffered from poorly standardized detection methods. Our liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is capable of simultaneous standardized analysis of most known polyamines. Liquid chromatography-tandem mass spectrometry has not previously been used in the differential diagnostics of ovarian tumors in postmenopausal women. MATERIALS AND METHODS: In this prospective study, postmenopausal women (n = 71) presenting with an adnexal mass and, as controls, women with genital prolapse or urinary incontinence scheduled for surgery (n = 22) were recruited in the study. For analysis of the polyamines, a morning urine sample was obtained before surgery. Preoperative serum CA125 concentrations were determined in the study group. RESULTS: Twenty-three women with benign and 37 with malignant ovarian tumors were eligible. Of all analyzed polyamines, only urinary N,N-diacetylspermine showed statistically significant differences between all groups except controls versus benign tumors. N,N-diacetylspermine was elevated in malignant versus benign tumors (P < 0.001), in high-grade versus low malignant potential tumors (P < 0.001), in stage III to IV versus stage I to II cancers (P < 0.001), and even in early-stage cancer (stage I-II) versus benign tumors (P = 0.017). N,N-diacetylspermine had better sensitivity (86.5%) but lower specificity (65.2%) for distinguishing benign and malignant ovarian tumors than CA125 with a cut-off value of 35 kU/L (sensitivity, 75.7%; specificity, 69.6%). CONCLUSIONS: Urinary N,N-diacetylspermine seems to be able to distinguish benign and malignant ovarian tumors as well as early and advanced stage, and low malignant potential and high-grade ovarian cancers from each other, respectively.
Subject(s)
Biogenic Polyamines/urine , Biomarkers, Tumor/urine , Ovarian Neoplasms/urine , Aged , Aged, 80 and over , Case-Control Studies , Chromatography, Liquid , Female , Humans , Middle Aged , Neoplasm Grading , Neoplasm Staging , Ovarian Neoplasms/pathology , Postmenopause/urine , Prospective Studies , Spermine/analogs & derivatives , Spermine/urine , Tandem Mass SpectrometryABSTRACT
BACKGROUND: Preoperative evaluation of ovarian tumors is challenging. This study was undertaken to evaluate the performance of conventional two-dimensional (2D) ultrasound and CA125 in predicting malignant or benign nature of pelvic masses, and to investigate if three-dimensional power Doppler (3DPD) ultrasound provides any added value. Ninety-six postmenopausal and four perimenopausal women with supposed ovarian tumors were examined by standardized 2D and 3DPD ultrasounds preoperatively. The tumors were evaluated using the risk of malignancy index (RMI), International Ovarian Tumors Analysis (IOTA) group simple rules, expert opinion, IOTA logistic regression model 2 (LR2) and 3D vascular indices, and were postoperatively compared to histopathological results. RESULTS: Ninety-eight tumors turned out to be ovarian in origin. Of these, 66 were benign and 32 malignant. RMI (cut-off value 200), simple rules, expert opinion and LR2 (cut-off value 25) were used to predict malignant nature of the tumors and had sensitivities of 71.9, 90.6, 87.5 and 90.6%, and specificities of 80.3, 84.6, 92.4 and 77.3%, respectively. When the 3D vascularization flow index (VFI) was added to RMI and LR2, the accuracy of the test improved from 77.6 to 81.4% and from 81.6 to 86.5%, respectively, at the expense of sensitivity, while VFI gave no added benefit for simple rules and expert opinion. Agreement between two examiners using expert opinion was good (Cohen's kappa = 0.89). CONCLUSIONS: The subjective opinion of an expert seems to be the most reliable method in assessing ovarian tumors, and the 3DPD indices seem to provide no significant added value.
