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Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2013

Open Access 01-12-2013 | Research

The use of HE4, CA125 and CA72-4 biomarkers for differential diagnosis between ovarian endometrioma and epithelial ovarian cancer

Authors: Emanuela Anastasi, Teresa Granato, Renato Falzarano, Paola Storelli, Adele Ticino, Luigi Frati, Pierluigi Benedetti Panici, Maria Grazia Porpora

Published in: Journal of Ovarian Research | Issue 1/2013

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Abstract

Background

Endometriosis is frequently associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish a panel of complementary biomarkers that could be helpful in the differential diagnosis between ovarian endometriosis or other ovarian benign masses and ovarian cancer.

Methods

Blood samples from 50 healthy women, 17 patients with benign ovarian tumors, 57 patients with ovarian endometrioma and 39 patients with ovarian cancer were analyzed and serum values were measured for the following biomarkers: CA125, HE4 and CA72-4.

Results

Serum CA125 concentration was elevated in both patients with ovarian endometriosis and ovarian cancer but not in patients with other benign ovarian masses. HE4 was never increased in patients with endometriosis or benign masses whereas it was significantly higher in all patients with ovarian cancer (p < 0.05). A marked difference in CA72-4 values was observed between women with ovarian cancer (67%) and those with endometriosis (p < 0.05).

Conclusions

The results of the study suggest that HE4 and CA72-4 determination is the best approach to confirm the benign nature of ovarian endometrioma in women with high CA125 levels.
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Literature
1.
Eskenazi B, Warner ML: Epidemiology of endometriosis. Obstet Gynecol Clin North Am 1997,24(2):235–258. 10.1016/S0889-8545(05)70302-8PubMedCrossRef
2.
3.
Porpora MG, Koninckx PR, Piazze J, Natili M, Colagrande S, Cosmi EV: Correlation between endometriosis and pelvic pain. J Am Assoc Gynecol Laparosc 1999,6(4):429–434. 10.1016/S1074-3804(99)80006-1PubMedCrossRef
4.
Porpora MG, Pallante D, Ferro A, Crisafi B, Bellati F, Benedetti Panici P: Pain and ovarian endometrioma recurrence after laparoscopic treatment of endometriosis: a long-term prospective study. Fertil Steril 2010,93(3):716–721. 10.1016/j.fertnstert.2008.10.018PubMedCrossRef
5.
Coccia ME, Rizzello F, Palagiano A, Scarselli G: Long-term follow-up after laparoscopic treatment for endometriosis: multivariate analysis of predictive factors for recurrence of endometriotic lesions and pain. Eur J Obstet Gynecol Reprod Biol 2011,157(1):78–83. 10.1016/j.ejogrb.2011.02.008PubMedCrossRef
6.
Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A, Saridogan E: On behalf of the ESHRE special interest group for endometriosis endometrium guideline development group. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005, 20: 2698–2704. 10.1093/humrep/dei135PubMedCrossRef
7.
Bordin L, Fiore C, Donà G, Andrisani A, Ambrosini G, Faggian D, Plebani M, Clari G, Armanini D: Evaluation of erythrocyte band 3 phosphotyrosine level, glutathione content, CA-125, and human epididymal secretory protein E4 as combined parameters in endometriosis. Fertil Steril 2010,94(5):1616–1621. 10.1016/j.fertnstert.2009.10.038PubMedCrossRef
8.
Escudero JM, Auge JM, Filella X, Torne A, Pahisa J, Molina R: Comparison of serum human epididymis protein 4 with cancer antigen 125 as a tumor marker in patients with malignant and nonmalignant diseases. Clin Chem 2011,57(11):1534–1544. 10.1373/clinchem.2010.157073PubMedCrossRef
9.
Gupta S, Agarwal A, Sekhon L, Krajcir N, Cocuzza M, Falcone T: Serum and peritoneal abnormalities in endometriosis: potential use as diagnostic markers. Minerva Ginecol 2006, 58: 527–551.PubMed
10.
Buamah P: Benign conditions associated with raised serum CA-125 concentration. J Surg Oncol 2000,75(4):264–265. 10.1002/1096-9098(200012)75:4<264::AID-JSO7>3.0.CO;2-QPubMedCrossRef
11.
McLemore MR, Aouizerat BE, Lee KA, Chen LM, Cooper B, Tozzi M, Miaskowski C: A comparison of the cyclic variation in serum levels of CA125 across the menstrual cycle using two commercial assays. Biol Res Nurs 2012,14(3):250–256. 10.1177/1099800411412766PubMedCrossRef
12.
Bast RC Jr, Klug TL, St John E, Jenison E, Niloff JM, Lazarus H, Berkowitz RS, Leavitt T, Griffiths CT, Parker L, Zurawski VR Jr, Knapp RC: A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med 1983,309(15):883–887. 10.1056/NEJM198310133091503PubMedCrossRef
13.
Tsoumpou I, Kyrgiou M, Gelbaya TA, Nardo LG: The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis. Fertil Steril 2009, 92: 75–87. 10.1016/j.fertnstert.2008.05.049PubMedCrossRef
14.
Raffi F, Metwally M, Amer S: The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. J Clin Endocrinol Metab 2012,97(9):3146–3154. 10.1210/jc.2012-1558PubMedCrossRef
15.
Vlahos NF, Economopoulos KP, Fotiou S: Endometriosis, in vitro fertilisation and the risk of gynaecological malignancies, including ovarian and breast cancer. Best Pract Res Clin Obstet Gynaecol 2010, 24: 39–50. 10.1016/j.bpobgyn.2009.08.004PubMedCrossRef
16.
Zygouris D, Leontara V, Makris GM, Chrelias C, Trakakis E, Christodoulaki C, Panagopoulos P: Endometrioid ovarian cancer arising from an endometriotic cyst in a young patient. Eur J Gynaecol Oncol 2012,33(3):324–325.PubMed
17.
Vasilakaki T, Skafida E, Arkoumani E, Grammatoglou X, Firfiris N, Manoloudaki K: Borderline clear cell adenofibroma of the ovary associated with ovarian endometriosis: a case report. Eur J GynaecolOncol 2012,33(2):230–232.
18.
Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, Steinhoff M, Messerlian G, Di Silvestro P, Granai CO, Bast RC Jr: The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol 2008,108(2):402–408. 10.1016/j.ygyno.2007.10.017PubMedCrossRef
19.
Moore RG, Miller MC, Steinhoff MM, Skates SJ, Lu KH, Lambert-Messerlian G, Bast RC Jr: Serum HE4 levels are less frequently elevated than CA125 in women with benign gynecologic disorders. Am J Obstet Gynecol 2012,206(4):351.PubMedCentralPubMed
20.
Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H, Setälä M, Härkki P, Jalkanen J, Fraser J, Mäkinen J, Auranen A, Poutanen M, Perheentupa A: Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer 2009,100(8):1315–1319. 10.1038/sj.bjc.6605011PubMedCentralPubMedCrossRef
21.
Nolen B, Velikokhatnaya L, Marrangoni A, De Geest K, Lomakin A, Bast RC Jr, Lokshin A: Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. Gynecol Oncol 2010,117(3):440–445. 10.1016/j.ygyno.2010.02.005PubMedCentralPubMedCrossRef
22.
Galgano MT, Hampton GM, Frierson HF Jr: Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol 2006,19(6):847–853.PubMed
23.
Nagy B Jr, Krasznai ZT, Balla H, Csobán M, Antal-Szalmás P, Hernádi Z, Kappelmayer J: Elevated human epididymis protein 4 concentrations in chronic kidney disease. Ann Clin Biochem 2012,49(4):377–380. 10.1258/acb.2011.011258PubMedCrossRef
24.
Lenhard MS, Nehring S, Nagel D, Mayr D, Kirschenhofer A, Hertlein L, Friese K, Stieber P, Burges A: Predictive value of CA125 and Ca72–4 in borderline ovarian tumors. Clin Chem Lab Med 2009,47(5):537–542.PubMedCrossRef
25.
Granato T, Midulla C, Longo F, Colaprisca B, Frati L, Anastasi E: Role of HE4, CA72–4, and CA125 in monitoring ovarian cancer. Tumor Biol 2012,33(5):1335–1339. 10.1007/s13277-012-0381-8CrossRef
26.
Manganaro L, Vittori G, Vinci V, Fierro F, Tomei A, Lodise P, Sollazzo P, Sergi ME, Bernardo S, Ballesio L, Marini M, Porpora MG: Beyond laparoscopy: 3-T magnetic resonance imaging in the evaluation of posteriorcul-de-sac obliteration. Magn Reson Imaging 2012,30(10):1432–1438. 10.1016/j.mri.2012.05.006PubMedCrossRef
27.
Manganaro L, Fierro F, Tomei A, Irimia D, Lodise P, Sergi ME, Vinci V, Sollazzo P, Porpora MG, Delfini R, Vittori G, Marini M: Feasibility of 3.0T pelvic MR imaging in the evaluation of endometriosis. Eur J Radiol 2012,81(6):1381–1387. 10.1016/j.ejrad.2011.03.049PubMedCrossRef
28.
American Society for Reproductive Medicine: Revised American society for reproductive medicine classification of endometriosis: 1996. Fertil Steril 1997,67(5):817–821. 10.1016/S0015-0282(97)81391-XCrossRef
29.
Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Pecorelli S, Beller U: Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006,95(Suppl 1):S161–92.PubMedCrossRef
30.
DeLong ER, DeLong DM, Clarke-Pearson DL: Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988,44(3):837–845. 10.2307/2531595PubMedCrossRef
31.
Van Holsbeke C, Van Calster B, Guerriero S, Savelli L, Paladini D, Lissoni AA, Czekierdowski A, Fischerova D, Zhang J, Mestdagh G, Testa AC, Bourne T, Valentin L, Timmerman D: Endometriomas: their ultrasound characteristics. Ultrasound Obstet Gynecol 2010,35(6):730–740.PubMed
32.
Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, et al.: Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies. Lancet Oncol 2012, 13: 385–394. 10.1016/S1470-2045(11)70404-1PubMedCentralPubMedCrossRef
33.
Bast RC Jr, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB: CA 125: the past and the future. Int J Biol Markers 1998,13(4):179–187.PubMed
34.
Anastasi E, Granato T, Coppa A, Manganaro L, Giannini G, Comploj S, Frati L, Midulla C: HE4 in the differential diagnosis of a pelvic mass: a case report. Int J Mol Sci 2011,12(1):627–632.PubMedCentralPubMedCrossRef
35.
Yamashita S, Tokuishi K, Hashimoto T, Moroga T, Kamei M, Ono K, Miyawaki M, Takeno S, Chujo M, Yamamoto S, Kawahara K: Prognostic significance of HE4 expression in pulmonary adenocarcinoma. Tumour Biol 2011,32(2):265–271. 10.1007/s13277-010-0118-5PubMedCrossRef
36.
Hamed EO, Ahmed H, Sedeek OB, Mohammed AM, Abd-Alla AA, Abdel Ghaffar HM: Significance of HE4 estimation in comparison with CA125 in diagnosis of ovarian cancer and assessment of treatment response. Diagn Pathol 2013, 8: 11. 10.1186/1746-1596-8-11PubMedCentralPubMedCrossRef
37.
Anastasi E, Granato T, Marchei G, Viggiani V, Colaprisca B, Comploj S, Reale M, Frati L, Midulla C: Ovarian tumor marker HE4 is differently expressed during the phases of the menstrual cycle in healthy young women. Tumour Biol 2010,31(5):411. 10.1007/s13277-010-0049-1PubMedCrossRef
38.
Hallamaa M, Suvitie P, Huhtinen K, Matomäki J, Poutanen M, Perheentupa A: Serum HE4 concentration is not dependent on menstrual cycle or hormonal treatment among endometriosis patients and healthy premenopausal women. Gynecol Oncol 2012, 125: 667–672. 10.1016/j.ygyno.2012.03.011PubMedCrossRef
39.
Bolstad N, Øijordsbakken M, Nustad K, Bjerne J: Human epididymis protein reference limits and natural variation in a Nordic reference population. Tumor Biol 2012, 33: 141–148. 10.1007/s13277-011-0256-4CrossRef
Metadata
Title
The use of HE4, CA125 and CA72-4 biomarkers for differential diagnosis between ovarian endometrioma and epithelial ovarian cancer
Authors
Emanuela Anastasi
Teresa Granato
Renato Falzarano
Paola Storelli
Adele Ticino
Luigi Frati
Pierluigi Benedetti Panici
Maria Grazia Porpora
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2013
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/1757-2215-6-44

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