Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) – a study of the TOC Consortium
Tóm tắt
Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.
Tài liệu tham khảo
Denkert C, Dietel M: Borderline tumors of the ovary and peritoneal implants. Verh Dtsch Ges Pathol 2005, 89: 84–91.
Coumbos A, Sehouli J, Chekerov R, Schadel D, Oskay-Oezcelik G, Lichtenegger W, Kuehn W: North Eastern Society of Gynecological Oncology (NOGGO). Clinical management of borderline tumors of the ovary: results of a multicentre survey of 323 clinics in Germany. BR J Cancer 2009,100(11):1731–1738. 10.1038/sj.bjc.6605065
Avril S, Hahn E, Specht K, Hauptmann S, Höss C, Kiechle M, Höfler H, Schmalfeldt B: Histopathologic features of ovarian borderline tumors are not predictive of clinical outcome. Gynecol Oncol 2012,127(3):516–524. doi:10.1016/j.ygyno.2012.08.027. Epub 2012 Sep 10.1016/j.ygyno.2012.08.027
Du Bois A, Ewald-Riegler N, Du Bois O, Harter P: Borderline tumors of the Ovary – A Systematic Review. Geburtsh Frauenheilk 2009, 69: 807–833. 10.1055/s-0029-1186007
Uzan C, Dufeu-Lefebvre M, Fauvet R, Gouy S, Duvillard P, Darai E, Morice P: Management and prognosis of borderline ovarian Brenner tumors. Int J Gynecol Cancer 2012,22(8):1332–1336. 10.1097/IGC.0b013e318267db2f
Sherman ME, Mink PJ, Curtis R, Cote TR, Brooks S, Hartge P, Devesa S: Survival among women with borderline ovarian tumors and ovarian carcinoma: a population-based analysis. Cancer 2004,100(5):1045–1052. 10.1002/cncr.20080
Yokoyama Y, Moriya T, Takano T, Shoji T, Takahashi O, Nakahara K, Yamada H, Yaegashi N, Okamura K, Izutsu T, Sugiyama T, Tanaka T, Kurachi H, Sato A, Tase T, Mizunuma H: Clinical outcome and risk factors for recurrence in borderline ovarian tumours. Br J Cancer 2006,94(11):1586–1591.
Skírnisdóttir I, Garmo H, Wilander E, Holmberg L: Borderline ovarian tumors in Sweden 1960–2005: trends in incidence and age at diagnosis compared to ovarian cancer. Int J Cancer 2008,123(8):1897–1901. doi:10.1002/ijc.2374 10.1002/ijc.23724
Tropé CG, Kristensen G, Makar A: Surgery for borderline tumor of the ovary. Semin Surg Oncol 2000,19(1):69–75. 10.1002/1098-2388(200007/08)19:1<69::AID-SSU11>3.0.CO;2-E
Schmaldfeldt B, Pfisterer J: Interdisziplinäre S2k-Leitlinie für die Diagnostik und Therapie maligner Ovarialtumoren. In Zuckschwerdt Verlag: 1 Edited by: Auflage. 2007. KO.d.A.G.O. e.V
Kaern J, Tropé CG, Abeler VM: A retrospective study of 370 borderline tumors of the ovary treated at the Norwegian Radium Hospital from 1970 to 1982. A review of clinicopathologic features and treatment modalities. Cancer 1993,71(5):1810–20. 10.1002/1097-0142(19930301)71:5<1810::AID-CNCR2820710516>3.0.CO;2-V
du Bois A, Ewald-Riegler N, de Gregorio N, Reuss A, Mahner S, Fotopoulou C, Kommoss F, Schmalfeldt B, Hilpert F, Fehm T, Burges A, Meier W, Hillemanns P, Hanker L, Hasenburg A, Strauss HG, Hellriegel M, Wimberger P, Keyver-Paik MD, Baumann K, Canzler U, Wollschlaeger K, Forner D, Pfisterer J, Schröder W, Münstedt K, Richter B, Kommoss S, Hauptmann S: Arbeitsgmeinschaft Gynäkologische Onkologie (AGO) Study Group. Borderline tumours of the ovary: A cohort study of the Arbeitsgmeinschaft Gynäkologische Onkologie (AGO) Study Group. Eur J Cancer 2013,49(8):1905–1914. 10.1016/j.ejca.2013.01.035
Hertlein L, Stieber P, Kirschenhofer A, Fürst S, Mayr D, Hofmann K, Krocker K, Nagel D, Lenhard M, Burges A: Human epididymis protein 4 (HE4) in benign and malignant diseases. Clin Chem Lab Med 2012. doi:10.1515/cclm-2012–0097
Bast RC Jr, Badgwell D, Lu Z, Marquez R, Rosen D, Liu J, Baggerly KA, Atkinson EN, Skates S, Zhang Z, Lokshin A, Menon U, Jacobs I, Lu K: New tumor markers: CA125 and beyond. Int J Gynecol Cancer 2005,15(3):274–281.
Moore RG, Miller MC, Eklund EE, Lu KH, Bast RC Jr, Lambert-Messerlian G: Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age. Am J. Obstet Gynecol 2012,206(4):349. e1–7. doi:10.1016/j.ajog.2011.12.028. Epub 2011 Dec 30
Galgano MT, Hampton GM, Frierson HF Jr: Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol 2006,19(6):847–53.
Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, Hecht JL: Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous endometrioid ovarian carcinomas. Cancer Res 2005,65(6):2162–9. 10.1158/0008-5472.CAN-04-3924
Holcomb K, Vucetic Z, Miller MC, Knapp RC: Human epididymis protein 4 offers a superior specificity in the differentiation of benign and malignant adnexal masses in premenopausal women. Am J Obstet Gynecol 2011, 205: 358. e1–6
Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ, Gajewski W, Kurman R, Bast RC Jr, Skates SJ: 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. Epub 2008 Oct 12 10.1016/j.ygyno.2008.08.031
Moore RG, Miller MC, Disilvestro P, Landrum LM, Gajewski W, Ball JJ, Skates SJ: Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pelvic mass. Obstet Gynecol 2011,118(2 Pt 1):280–8. doi:10.1097/AOG.0b013e318224fce2
Lenhard M, Stieger P, Hertlein L, Kirschenhofer A, Fürst S, Mayr D, Nagel D, Hofmann K, Krocker K, Burges A: The diagnostic accuracy of two human epididymis protein 4 (HE4) testing systems in combination with CA125 in the differential diagnosis of ovarian masses. Clin Chem Lab Med 2011,49(12):2081–8.
Hori SS, Gambhir SS: Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations. Sci Transl Med 2011,3(109):109–116. doi:10.1126/scitranslmed.3003110
Fischerova D, Zikan M, Dundr P, Cibula D: Diagnosis, treatment, and follow-up of borderline ovarian tumors. Oncologist 2012,17(12):1515–33. 10.1634/theoncologist.2012-0139
Romero I, Bast RC Jr: Minireview: human ovarian cancer: biology, current management, and paths to personalizing therapy. Endocrinology 2012,153(4):1593–602. doi:10.1210/en.2011–2123 10.1210/en.2011-2123
Morice P, Camatte S, Rey A, Atallah D, Lhommé C, Pautier P, Pomel C, Coté JF, Haie-Meder C, Duvillard P, Castaigne D: Prognostic factors for patients with advanced stage serous borderline tumours of the ovary. Ann Oncol 2003,14(4):592–8. 10.1093/annonc/mdg173
Trillsch F, Mahner S, Ruetzel J, Harter P, Ewald-Riegler N, Jaenicke F, du Bois A: Clinical management of borderline ovarian tumors. Expert Rev Anticancer Ther 2010,10(7):1115–24. doi:10.1586/era.10.90 10.1586/era.10.90
Molina R, Escudero JM, Augé JM, Xavier F, Laura F, Aureli T, Jose L, Jaume P: HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases. Tumour Biol 2011,32(6):1087–1095. Published online 2011 August 24. doi:10.1007/s13277–011–0204–3) 10.1007/s13277-011-0204-3
Kong SY, Han MH, Yoo HJ, Hwang JH, Lim MC, Seo SS, Yoo CW, Kim JH, Park SY, Kang S: Serum HE4 level is an independent prognostic factor in epithelial ovarian cancer. Ann Surg Oncol 2012,19(5):1707–12. doi:10.1245/s10434–011–1943–5 10.1245/s10434-011-1943-5
Shih KK, Zhou Q, Huh J, Morgan JC, Iasonos A, Aghajanian C, Chi DS, Barakat RR, Abu-Rustum NR: Risk factors for recurrence of ovarian borderline tumors. Gynecol Oncol 2011,120(3):480–4. doi:10.1016/j.ygyno.2010.11.016. Epub 2010 Dec 10 10.1016/j.ygyno.2010.11.016
Van Gorp T, Veldman J, Van Calster B, Cadron I, Leunen K, Amant F, Timmerman D, Vergote I: Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses. Eur J Cancer 2012,48(11):1649–56. doi:10.1016/j.ejca.2011.12.003 10.1016/j.ejca.2011.12.003
Fischerova D, Franchi D, Testa A, Valentin LI, Savelli L, Lissoni A, Fruscio R, Van Holsbeke C, De Jonge E, VanHuffel S, Bourne T, Van Calster B, Amant F, Timmerman D: Ultrasound in diagnosis of new and borderline ovarian tumors. Ultrasound Obstet Gynecol 2010,36(1):1–2. Abstract OC01.03 10.1002/uog.7714
Gotlieb WH, Soriano D, Achiron R, Zalel Y, Davidson B, Kopolovic J, Novikov I, Ben-Baruch G: CA 125 measurement and ultrasonography in borderline tumors of the ovary. Am J Obstet Gynecol 2000,183(3):541–6. 10.1067/mob.2000.105940
Nassir M, Darb-Esfahani S, Richter R, Chekerov R, Hall C, Muallem MZ, Denkert C, Stamatian F, Fotopoulou C, Sehouli J, Braicu EI: HE4 Tissue Expression in Borderline Ovarian Tumors: A Pilot Study by the Tumorbank Ovarian Cancer Network. Anticancer Res 2013,33(4):1673–7.
Kaijser J, Van Gorp T, Smet ME, Van Holsbeke C, Sayasneh A, Epstein E, Bourne T, Vergote I, Van Calster B, Timmerman D: Are serum HE4 or ROMA scores useful to experienced examiners for improving characterization of adnexal masses after transvaginal ultrasonography? Ultrasound Obstet Gynecol 2014,43(1):89–97. doi:10.1002/uog.12551 10.1002/uog.12551
Urban N, Thorpe J, Karlan BY, McIntosh MW, Palomares MR, Daly MB, Paley P, Drescher CW: Interpretation of single and serial measures of HE4 and CA125 in asymptomatic women at high risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev 2012,21(11):2087–94. 10.1158/1055-9965.EPI-12-0616
Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, Lewis S, Davies S, Philpott S, Lopes A, Godfrey K, Oram D, Herod J, Williamson K, Seif MW, Scott I, Mould T, Woolas R, Murdoch J, Dobbs S, Amso NN, Leeson S, Cruickshank D, McGuire A, Campbell S, Fallowfield L, Singh N, Dawnay A, Skates SJ, Parmar M, et al.: Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 2009,10(4):327–40. 10.1016/S1470-2045(09)70026-9