Current Women`s Health Reviews

Author(s): Emily Penick* and Victoria Olowu

DOI: 10.2174/1573404813666171101163653

Utilization of Tumor Markers in Adnexal Masses: A Review of Current Literature

Page: [3 - 11] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Adnexal masses are a common presenting concern among women of all age groups. While the majority of adnexal masses are benign, the differentiation of a mass and diagnosis of malignancy can present a dilemma. The use of laboratory studies and tumor markers, which can be obtained through minimally invasive means, can aid in the diagnosis of a mass or the decision to refer a patient to a specialist.

Objective: This review provides information on current available tumor markers, their use in the diagnosis of various adnexal masses and tumors, a review on current biomarker panels, and the role these results play in treating pre- and postmenopausal patients with adnexal masses.

Results: Many tumor markers exist; however, the majority of markers are not specific to one tumor or cancer. Many benign conditions also cause elevations in tumor markers, which can make distinguishing benign and malignant conditions difficult. In recent years, the development of biomarker panels has served to improve diagnostic accuracy when dealing with an adnexal mass and algorithms have been developed to aid with triaging a patient to continued observation versus referral to a specialist.

Conclusion: It is important to merge clinical and laboratory data together when diagnosing and managing any patient with an adnexal mass given the many benign and malignant conditions that can cause elevations in tumor markers.

Keywords: Adnexal masses, tumor markers, adnexal masses diagnosis, malignancy, postmenopausal patients, cancer antigen.

Graphical Abstract

[1]
American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology. Evaluation and management of adnexal masses. Practice Bulletin No. 174. Obstet Gynecol 2016; 128: e210-26.
[2]
Schorge JO, Modesitt SC, Coleman RL, et al. SGO White Paper on ovarian cancer: etiology, screening and surveillance. Gynecol Oncol 2010; 119(1): 7-17.
[3]
"Tumor Markers." National Cancer Institute; 2015. Available at. https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/ tumor-markers-fact-sheet (Accessed on: November 14, 2016).
[4]
Soletormos G, Duffy MJ, Othman Abu Hassan S, et al. Clinical use of cancer biomarkers in epithelial ovarian cancer: Updated guidelines from the European group on tumor markers. Int J Gynecol Cancer 2016; 26(1): 43-51.
[5]
Sharma S. Tumor markers in clinical practice: General principles and guidelines. Indian J Med Paediatr Oncol 2009; 30(1): 1-8.
[6]
Johnson CC, Kessel B, Riley TL, et al. The epidemiology of CA-125 in women without evidence of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) screening trial. Gynecol Oncol 2008; 110(3): 383-9.
[7]
Bast RC Jr, Klug TL, St John E, et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med 1983; 309(15): 883-7.
[8]
Kitawaki J, Ishihara H, Koshiba H, et al. Usefulness and limits of CA-125 in diagnosis of endometriosis without associated ovarian endometriomas. Hum Reprod 2005; 20(7): 1999-2003.
[9]
Graham L. ACOG releases guidelines on management of adnexal masses. Am Fam Physician 2008; 77(9): 1320-3.
[10]
Karlsen MA, Sandhu N, Hogdall C, 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.
[11]
van den Akker PA, Aalders AL, Snijders MP, et al. Evaluation of the Risk of Malignancy Index in daily clinical management of adnexal masses. Gynecol Oncol 2010; 116(3): 384-8.
[12]
Hakansson F, Hogdall EV, Nedergaard L, et al. Risk of malignancy index used as a diagnostic tool in a tertiary centre for patients with a pelvic mass. Acta Obstet Gynecol Scand 2012; 91(4): 496-502.
[13]
Perkins GL, Slater E, Sanders G, Prichard J. Serum tumor markers. Am Fam Physician 2003; 68(6): 1075-82.
[14]
Liu Z, Zhang Y, Niu Y, et al. A systematic review and meta-analysis of diagnostic and prognostic serum biomarkers of colorectal cancer. PLoS One 2014; 9(8): e103910.
[15]
Hogdall EV, Christensen L, Kjaer SK, et al. Protein expression levels of carcinoembryonic antigen (CEA) in Danish ovarian cancer patients: from the Danish 'MALOVA’ovarian cancer study. Pathology 2008; 40(5): 487-92.
[16]
Solvsten Sorenson S, Jul Mosgaard B. Combination of cancer antigen 125 and carcinoembryonic antigen can improve ovarian cancer diagnosis. Dan Med Bull 2011; 58(11): A4331.
[17]
Pectasides D, Pectasides E, Kassanos D. Germ cell tumors of the ovary. Cancer Treat Rev 2008; 34(5): 427-41.
[18]
Fowler JE Jr, Platoff GE, Kubrock CA, Stutzman RE. Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone. Cancer 1982; 49(1): 136-9.
[19]
Kelleher CM, Goldstein AM. Adnexal masses in children and adolescents. Clin Obstet Gynecol 2015; 58(1): 76-92.
[20]
Martin LJ, Zieve D. Lactate dehydrogenase test NIH, US National Library of Medicine, Medline Plus A.D.A.M. Editorial team; 2016.
[21]
de Kretser DM, Hedger MP, Loveland KL, Phillips DJ. Inhibins, activins and follistatin in reproduction. Hum Reprod Update 2002; 8(6): 529-41.
[22]
Robertson DM, Pruysers E, Jobling T. Inhibin as a diagnostic marker for ovarian cancer. Cancer Lett 2007; 249(1): 14-7.
[23]
Robertson DM, Pruysers E, Burger HG, Jobling T, McNeilage J, Healy D. Inhibins and ovarian cancer. Mol Cell Endocrinol 2004; 225(1-2): 65-71.
[24]
Mom CH, Engelen MJ, Willemse PH, et al. Granulosa cell tumors of the ovary: the clinical value of serum inhibin A and B levels in a large single center cohort. Gynecol Oncol 2007; 105(2): 365-72.
[25]
Robertson DM, Stephenson T, Pruysers E, et al. Characterization of inhibin forms and their measurement by an inhibin alpha-subunit ELISA in serum from postmenopausal women with ovarian cancer. J Clin Endocrinol Metab 2002; 87(2): 816-24.
[26]
Sehested A, Juul AA, Andersson AM, et al. Serum inhibin A and inhibin B in healthy prepubertal, pubertal, and adolescent girls and adult women: relation to age, stage of puberty, menstrual cycle, follicle-stimulating hormone, luteinizing hormone, and estradiol levels. J Clin Endocrinol Metab 2000; 85(4): 1634-40.
[27]
Lappohn RE, Burger HG, Bouma J, Bangah M, Krans M. Inhibin as a marker for granulosa cell tumor. Acta Obstet Gynecol Scand Suppl 1992; 155: 61-5.
[28]
Schumer ST. Granulosa cell tumor of the ovary. J Clin Oncol 2003; 21(6): 1180-9.
[29]
Sofronescu A, Staros E. "Estradiol" In Drugs and Diseases Available at: https://emedicine.medscape.com/article/2089003-overview (Accessed on: March 1, 2017).
[30]
Scharl A, Crombach G, Vierbuchen M, Gohring U, Gottert T, Holt JA. Antigen CA 19-9: presence in mucosa of nondiseased mullerian duct derivatives and marker for differentiation in their carcinomas. Obstet Gynecol 1991; 77(4): 580-5.
[31]
Santotoribio JD, Garcia-de la Torre A, Canavate-Solano C, Arce-Matute F, Sanchez-del Pino MJ, Perez-Ramos S. Cancer antigens 19.9 and 125 as tumor markers in patients with mucinous ovarian tumors. Eur J Gynaecol Oncol 2016; 37(1): 26-9.
[32]
Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19: 230-5.
[33]
Moore RG, Brown AK, Miller MC, et al. Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus. Gynecol Oncol 2008; 110(2): 196-201.
[34]
Simmons AR, Baggerly K, Bast RC Jr. The emerging role of HE4 in the evaluation of epithelial ovarian and endometrial carcinomas. Oncology (Williston Park) 2013; 27(6): 548-56.
[35]
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.
[36]
Drapkin R, von Horsten HH, Lin Y, 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.
[37]
Lin J, Qin J, Sangvatanakul V. Human epididymis protein 4 for differential diagnosis between benign gynecologic disease and ovarian cancer: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2013; 167(1): 81-5.
[38]
Kondalsamy-Chennakesavan S, Hackethal A, Bowtell D. Australian Ovarian Cancer Study G, Obermair A. Differentiating stage 1 epithelial ovarian cancer from benign ovarian tumours using a combination of tumour markers HE4, CA125, and CEA and patient’s age. Gynecol Oncol 2013; 129(3): 467-71.
[39]
Angioli R, Plotti F, Capriglione S, et al. The role of novel biomarker HE4 in endometrial cancer: a case control prospective study. Tumour Biol 2013; 34(1): 571-6.
[40]
U.S. Food and Drug Administration. OVA1 Next Generation. 510(k) substantial equivalence determination decision summary.Silver Spring (MD): FDA; 2016. Available at:. http://www. accessdata.fda.gov/cdrh_ docs/reviews/K150588.pdf (Accessed on: March 1, 2017)..
[41]
U.S. Food and Drug Administration. ROMATM (HE4 EIA + Architect CA 125 10TM). 510(k) summary. Silver Spring (MD): FDA; 2011. Available at:. http:// www.accessdata.fda.gov/cdrh_ docs/pdf10/K103358.pdf (Accessed on: March 1, 2017).
[42]
Bristow RE, Smith A, Zhang Z, et al. Ovarian malignancy risk stratification of the adnexal mass using a multivariate index assay. Gynecol Oncol 2013; 128(2): 252-9.
[43]
Ueland FR, Desimone CP, Seamon LG, et al. Effectiveness of a multivariate index assay in the preoperative assessment of ovarian tumors. Obstet Gynecol 2011; 117(6): 1289-97.
[44]
Moore RG, McMeekin DS, Brown AK, 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.
[45]
Moore RG, Miller MC, Disilvestro P, et al. 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.
[46]
Skates SJ. Ovarian cancer screening: development of the risk of ovarian cancer algorithm (ROCA) and ROCA screening trials. Int J Gynecol Cancer 2012; 22(Suppl. 1): S24-6.
[47]
Menon U, Ryan A, Kalsi J, et al. Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom collaborative trial of ovarian cancer screening. J Clin Oncol 2015; 33(18): 2062-71.
[48]
Van Calster B, Van Hoorde K, Valentin L, et al. Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study. BMJ 2014; 349: g5920.
[49]
Sayasneh A, Wynants L, Preisler J, et al. Multicentre external validation of IOTA prediction models and RMI by operators with varied training. Br J Cancer 2013; 108(12): 2448-54.
[50]
Timmerman D, Testa AC, Bourne T, et al. Logistic regression model to distinguish between the benign and malignant adnexal mass before surgery: a multicenter study by the International Ovarian Tumor Analysis Group. J Clin Oncol 2005; 23(34): 8794-801.
[51]
Kaijser J, Bourne T, Valentin L, et al. Improving strategies for diagnosing ovarian cancer: a summary of the International Ovarian Tumor Analysis (IOTA) studies. Ultrasound Obstet Gynecol 2013; 41(1): 9-20.
[52]
Van Holsbeke C, Van Calster B, Bourne T, et al. External validation of diagnostic models to estimate the risk of malignancy in adnexal masses. Clin Cancer Res 2012; 18(3): 815-25.
[53]
Barroilhet L, Vitonis A, Shipp T, Muto M, Benacerraf B. Sonographic predictors of ovarian malignancy. J Clin Ultrasound 2013; 41(5): 269-74.
[54]
Goff BA, Mandel L, Muntz HG, Melancon CH. Ovarian carcinoma diagnosis. Cancer 2000; 89(10): 2068-75.
[55]
Committee on Gynecologic Practice, Society of Gynecologic Oncology. The role of the obstetrician–gynecologist in the early detection of epithelial ovarian cancer in women at average risk. Committee Opinion No. 716. Obstet Gynecol 2017; 130: e146-9.
[56]
American College of Obstetricians and Gynecologists. Practice Advisory: FDA Issues Safety Communication on Screening Tests for Ovarian Cancer. 2016.
[57]
American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins. Hereditary Breast and Ovarian Cancer Syndrome. Obstet Gynecol 2009; 113.
[58]
Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet 2014; 384(9951): 1376-88.
[59]
Rustin GJ, Vergote I, Eisenhauer E, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer 2011; 21(2): 419-23.