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Erschienen in: Tumor Biology 2/2016

09.09.2015

Development of a multi-marker model combining HE4, CA125, progesterone, and estradiol for distinguishing benign from malignant pelvic masses in postmenopausal women

verfasst von: Pengjun Zhang, Chuanxin Wang, Liming Cheng, Peng Zhang, Lin Guo, Wanli Liu, Zhongying Zhang, Yanchun Huang, Qishui Ou, Xinyu Wen, Yaping Tian

Erschienen in: Tumor Biology | Ausgabe 2/2016

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Abstract

The purpose of this study was to evaluate HE4, CA125, progesterone (Prog), and estradiol (E2) for differentiating pelvic masses in postmenopausal women and aimed to build a multi-marker model which may improve the diagnostic value. HE4, CA125, Prog, and E2 were detected in 57 benign pelvic masses (BPM) and 92 epithelial ovarian cancer (EOC) patients. A total of 66.66 % of the BPM and EOC serum samples were used for building the differentiation model, and the remaining 33.33 % of the BPM and EOC serum samples were used for validation of the differentiation model. After comparing by Z score statistics, HE4 + CA125 + E2 model was chosen as the best multi-marker model. In the training group, the area under curve of the HE4 + CA125 + E2 model was 0.97 (0.93, 1.00), sensitivities of the model for distinguishing BPM from EOC, from early EOC, and from advanced EOC were 90.16, 86.21, and 95.65 %; specificities were 92.11, 92.11, and 92.11 %. In the validation group, sensitivities of HE4 + CA125 + E2 model for distinguishing BPM from EOC, from early EOC, and from advanced EOC were 96.77, 100.00, and 87.50 %, specificities were 84.21, 100.00, and 84.21 %. The multi-marker model showed significant improvement when compared to CA125 or HE4, and it might be an effective pelvic mass differentiation method.
Literatur
4.
Zurück zum Zitat Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005;65(6):2162–9. doi:10.1158/0008-5472.CAN-04-3924.CrossRefPubMed Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005;65(6):2162–9. doi:10.​1158/​0008-5472.​CAN-04-3924.CrossRefPubMed
5.
Zurück zum Zitat Hellstrom I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 2003;63(13):3695–700.PubMed Hellstrom I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 2003;63(13):3695–700.PubMed
6.
Zurück zum Zitat Ferraro S, Braga F, Lanzoni M, Boracchi P, Biganzoli EM, Panteghini M. Serum human epididymis protein 4 vs carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review. J Clin Pathol. 2013;66(4):273–81. doi:10.1136/jclinpath-2012-201031.CrossRefPubMed Ferraro S, Braga F, Lanzoni M, Boracchi P, Biganzoli EM, Panteghini M. Serum human epididymis protein 4 vs carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review. J Clin Pathol. 2013;66(4):273–81. doi:10.​1136/​jclinpath-2012-201031.CrossRefPubMed
9.
Zurück zum Zitat Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ, et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol. 2009;112(1):40–6. doi:10.1016/j.ygyno.2008.08.031.CrossRefPubMed Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ, et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol. 2009;112(1):40–6. doi:10.​1016/​j.​ygyno.​2008.​08.​031.CrossRefPubMed
10.
Zurück zum Zitat Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990;97(10):922–9.CrossRefPubMed Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990;97(10):922–9.CrossRefPubMed
11.
Zurück zum Zitat Moore RG, Jabre-Raughley M, Brown AK, Robison KM, Miller MC, Allard WJ, et al. Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass. Am J Obstet Gynecol. 2010;203(3):228 e1–6. doi:10.1016/j.ajog.2010.03.043.CrossRef Moore RG, Jabre-Raughley M, Brown AK, Robison KM, Miller MC, Allard WJ, et al. Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass. Am J Obstet Gynecol. 2010;203(3):228 e1–6. doi:10.​1016/​j.​ajog.​2010.​03.​043.CrossRef
12.
Zurück zum Zitat Karlsen MA, Sandhu N, Hogdall C, Christensen IJ, Nedergaard L, Lundvall L, et al. 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. Gynecol Oncol. 2012;127(2):379–83. doi:10.1016/j.ygyno.2012.07.106.CrossRefPubMed Karlsen MA, Sandhu N, Hogdall C, Christensen IJ, Nedergaard L, Lundvall L, et al. 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. Gynecol Oncol. 2012;127(2):379–83. doi:10.​1016/​j.​ygyno.​2012.​07.​106.CrossRefPubMed
13.
Zurück zum Zitat Montagnana M, Danese E, Ruzzenente O, Bresciani V, Nuzzo T, Gelati M, et al. The ROMA (Risk of Ovarian Malignancy Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful? Clin Chem Lab Med. 2011;49(3):521–5. doi:10.1515/CCLM.2011.075.CrossRefPubMed Montagnana M, Danese E, Ruzzenente O, Bresciani V, Nuzzo T, Gelati M, et al. The ROMA (Risk of Ovarian Malignancy Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful? Clin Chem Lab Med. 2011;49(3):521–5. doi:10.​1515/​CCLM.​2011.​075.CrossRefPubMed
15.
Zurück zum Zitat Lukanova A, Kaaks R. Endogenous hormones and ovarian cancer: epidemiology and current hypotheses. Cancer Epidemiol Biomarkers Prev. 2005;14(1):98–107.PubMed Lukanova A, Kaaks R. Endogenous hormones and ovarian cancer: epidemiology and current hypotheses. Cancer Epidemiol Biomarkers Prev. 2005;14(1):98–107.PubMed
17.
Zurück zum Zitat Han KH, Kim MK, Kim HS, Chung HH, Song YS. Protective effect of progesterone during pregnancy against ovarian cancer. J Cancer Prev. 2013;18(2):113–22.CrossRefPubMedPubMedCentral Han KH, Kim MK, Kim HS, Chung HH, Song YS. Protective effect of progesterone during pregnancy against ovarian cancer. J Cancer Prev. 2013;18(2):113–22.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Timmerman D, Valentin L, Bourne TH, Collins WP, Verrelst H, Vergote I. Terms, definitions and measurements to describe the sonographic features of adnexal tumors: a consensus opinion from the International Ovarian Tumor Analysis (IOTA) Group. Ultrasound Obstet Gynecol. 2000;16(5):500–5. doi:10.1046/j.1469-0705.2000.00287.x.CrossRefPubMed Timmerman D, Valentin L, Bourne TH, Collins WP, Verrelst H, Vergote I. Terms, definitions and measurements to describe the sonographic features of adnexal tumors: a consensus opinion from the International Ovarian Tumor Analysis (IOTA) Group. Ultrasound Obstet Gynecol. 2000;16(5):500–5. doi:10.​1046/​j.​1469-0705.​2000.​00287.​x.CrossRefPubMed
21.
Zurück zum Zitat Fearon WF, Gauri AJ, Myers J, Raxwal VK, Atwood JE, Froelicher VF. A comparison of treadmill scores to diagnose coronary artery disease. Clin Cardiol. 2002;25(3):117–22.CrossRefPubMed Fearon WF, Gauri AJ, Myers J, Raxwal VK, Atwood JE, Froelicher VF. A comparison of treadmill scores to diagnose coronary artery disease. Clin Cardiol. 2002;25(3):117–22.CrossRefPubMed
24.
26.
30.
Zurück zum Zitat Anton C, Carvalho FM, Oliveira EI, Maciel GA, Baracat EC, Carvalho JP. A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses. Clinics (Sao Paulo). 2012;67(5):437–41.CrossRef Anton C, Carvalho FM, Oliveira EI, Maciel GA, Baracat EC, Carvalho JP. A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses. Clinics (Sao Paulo). 2012;67(5):437–41.CrossRef
32.
Zurück zum Zitat Ruggeri G, Bandiera E, Zanotti L, Belloli S, Ravaggi A, Romani C, et al. HE4 and epithelial ovarian cancer: comparison and clinical evaluation of two immunoassays and a combination algorithm. Clin Chim Acta. 2011;412(15-16):1447–53. doi:10.1016/j.cca.2011.04.028.CrossRefPubMed Ruggeri G, Bandiera E, Zanotti L, Belloli S, Ravaggi A, Romani C, et al. HE4 and epithelial ovarian cancer: comparison and clinical evaluation of two immunoassays and a combination algorithm. Clin Chim Acta. 2011;412(15-16):1447–53. doi:10.​1016/​j.​cca.​2011.​04.​028.CrossRefPubMed
33.
37.
Zurück zum Zitat Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez Lira-Lira G, Escudero-De los Rios P, Salmeron-Castro J, Hernandez-Avila M. Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico. Cancer Res. 1999;15:3658–62. Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez Lira-Lira G, Escudero-De los Rios P, Salmeron-Castro J, Hernandez-Avila M. Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico. Cancer Res. 1999;15:3658–62.
38.
Zurück zum Zitat Liao J, Ding D, Sun C, Weng D, Meng L, Chen G, et al. Polymorphisms of progesterone receptor and ovarian cancer risk: a systemic review and meta-analysis. J Obstet Gynaecol Res. 2015;41(2):178–87. doi:10.1111/jog.12519.CrossRefPubMed Liao J, Ding D, Sun C, Weng D, Meng L, Chen G, et al. Polymorphisms of progesterone receptor and ovarian cancer risk: a systemic review and meta-analysis. J Obstet Gynaecol Res. 2015;41(2):178–87. doi:10.​1111/​jog.​12519.CrossRefPubMed
39.
Zurück zum Zitat Liu T, Chen L, Sun X, Wang Y, Li S, Yin X, et al. Progesterone receptor PROGINS and +331G/A polymorphisms confer susceptibility to ovarian cancer: a meta-analysis based on 17 studies. Tumour Biol. 2014;35(3):2427–36. doi:10.1007/s13277-013-1322-x.CrossRefPubMed Liu T, Chen L, Sun X, Wang Y, Li S, Yin X, et al. Progesterone receptor PROGINS and +331G/A polymorphisms confer susceptibility to ovarian cancer: a meta-analysis based on 17 studies. Tumour Biol. 2014;35(3):2427–36. doi:10.​1007/​s13277-013-1322-x.CrossRefPubMed
43.
Zurück zum Zitat McDonnel AC, Van Kirk EA, Isaak DD, Murdoch WJ. Inhibitory effects of progesterone on plasma membrane fluidity and tumorigenic potential of ovarian epithelial cancer cells. Exp Biol Med (Maywood). 2003;228(3):308–14. McDonnel AC, Van Kirk EA, Isaak DD, Murdoch WJ. Inhibitory effects of progesterone on plasma membrane fluidity and tumorigenic potential of ovarian epithelial cancer cells. Exp Biol Med (Maywood). 2003;228(3):308–14.
44.
47.
Zurück zum Zitat Laviolette LA, Garson K, Macdonald EA, Senterman MK, Courville K, Crane CA, et al. 17beta-estradiol accelerates tumor onset and decreases survival in a transgenic mouse model of ovarian cancer. Endocrinology. 2010;151(3):929–38. doi:10.1210/en.2009-0602.CrossRefPubMed Laviolette LA, Garson K, Macdonald EA, Senterman MK, Courville K, Crane CA, et al. 17beta-estradiol accelerates tumor onset and decreases survival in a transgenic mouse model of ovarian cancer. Endocrinology. 2010;151(3):929–38. doi:10.​1210/​en.​2009-0602.CrossRefPubMed
48.
Zurück zum Zitat Choi KC, Kang SK, Tai CJ, Auersperg N, Leung PC. Estradiol up-regulates antiapoptotic Bcl-2 messenger ribonucleic acid and protein in tumorigenic ovarian surface epithelium cells. Endocrinology. 2001;142(6):2351–60. doi:10.1210/endo.142.6.8144.PubMed Choi KC, Kang SK, Tai CJ, Auersperg N, Leung PC. Estradiol up-regulates antiapoptotic Bcl-2 messenger ribonucleic acid and protein in tumorigenic ovarian surface epithelium cells. Endocrinology. 2001;142(6):2351–60. doi:10.​1210/​endo.​142.​6.​8144.PubMed
49.
Zurück zum Zitat Mabuchi S, Ohmichi M, Kimura A, Nishio Y, Arimoto-Ishida E, Yada-Hashimoto N, et al. Estrogen inhibits paclitaxel-induced apoptosis via the phosphorylation of apoptosis signal-regulating kinase 1 in human ovarian cancer cell lines. Endocrinology. 2004;145(1):49–58. doi:10.1210/en.2003-0792.CrossRefPubMed Mabuchi S, Ohmichi M, Kimura A, Nishio Y, Arimoto-Ishida E, Yada-Hashimoto N, et al. Estrogen inhibits paclitaxel-induced apoptosis via the phosphorylation of apoptosis signal-regulating kinase 1 in human ovarian cancer cell lines. Endocrinology. 2004;145(1):49–58. doi:10.​1210/​en.​2003-0792.CrossRefPubMed
50.
Zurück zum Zitat Kirilovas D, Schedvins K, Naessen T, Von Schoultz B, Carlstrom K. Conversion of circulating estrone sulfate to 17beta-estradiol by ovarian tumor tissue: a possible mechanism behind elevated circulating concentrations of 17beta-estradiol in postmenopausal women with ovarian tumors. Gynecol Endocrinol. 2007;23(1):25–8.CrossRefPubMed Kirilovas D, Schedvins K, Naessen T, Von Schoultz B, Carlstrom K. Conversion of circulating estrone sulfate to 17beta-estradiol by ovarian tumor tissue: a possible mechanism behind elevated circulating concentrations of 17beta-estradiol in postmenopausal women with ovarian tumors. Gynecol Endocrinol. 2007;23(1):25–8.CrossRefPubMed
Metadaten
Titel
Development of a multi-marker model combining HE4, CA125, progesterone, and estradiol for distinguishing benign from malignant pelvic masses in postmenopausal women
verfasst von
Pengjun Zhang
Chuanxin Wang
Liming Cheng
Peng Zhang
Lin Guo
Wanli Liu
Zhongying Zhang
Yanchun Huang
Qishui Ou
Xinyu Wen
Yaping Tian
Publikationsdatum
09.09.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4037-3

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