Cancer antigens 19.9 and 125 as tumor markers in patients with mucinous ovarian tumors

Purpose of investigation: To determine the accuracy of carcinoembryonic antigen (CEA), cancer antigen (CA) 15.3, CA 19.9, and CA125 for diagnosis of mucinous ovarian cancer (MOC). Materials and Methods: Samples were collected preoperatively from patients with mucinous ovarian tumor. The following variables were analysed: CEA, CA 15.3, CA 19.9, and CA 125. After surgery, histology and stage were determined according to FIGO-classification. Patients were classified into two groups according to the diagnosis of ovarian biopsy: NOT MOC and MOC. Results: The authors studied 94 patients with ages between 15 and 80 years (median = 43). Eightytwo patients were NOT MOC (68 mucinous ovarian cystadenomas and 14 mucinous borderline ovarian tumors) and 12 were MOC. All MOC patients were in FIGO Stages I or II. No statistically significant differences were found between MOC and NOT MOC patients according to CEA and CA 15.3 (p > 0.05). All MOC patients had abnormal serum CA 19.9 and/or CA 125 levels. Using CA 19.9 and CA 125, we performed a linear regression formula CA 19.9 + 125 = 0.00102 x CA 19.9 + 0.00057 x CA 125. AUCs values were 0.862 (p = 0.0002), 0.829 (p = 0.0021), and 0.911 (p = 0.0001) for CA 19.9, CA 125, and CA 19.9 + 125, respectively. CA 19.9 + 125 exhibited 95.1 % specificity and 66.7% sensitivity, increased by 16.7% sensitivity compared with using only CA 19.9 or CA 125. Conclusions: Preoperative CA 19.9 and CA 125 levels showed high diagnosis efficacy to predict whether a mucinous ovarian tumour is benign or malignant. Using both markers simultaneously increases the sensitivity for diagnosis of MOC.

CEA; CA 15.3; CA 19.9; CA 125; Tumor markers; Mucinous ovarian cancer.

[1] Yurkovetsky Z., Skates S., Lomakin A., Nolen B., Pulsipher T., Modugno F., et al.: “Development of a multimarker assay for early detection of ovarian cancer”. J. Clin. Oncol., 2010, 28, 2159.

[2] Sung P.L, Chang Y.H., Chao K.C., Chuang C.M., Task Force on Systematic Review and Meta-analysis of Ovarian Cancer: “Global distribution pattern of histological subtypes of epithelial ovarian cancer: a database analysis and systematic review”. Gynecol. Oncol., 2014, 133, 147.

[3] Lee K.R., Tavassoli F.A., Prat J., Dietel M., Gersell D.J., Karseladze A.I., et al.: “WHO histological classification of tumours of the ovary”. In: Tavassoli F.A., Devilee P., (eds). Pathology and genetics of tumours of the breast and female genital organs. Lyon: IARC Press, 2003, 113.

[4] Nolen B., Marrangoni A., Velikokhatnaya L., Prosser D., Winans M., Gorelik E., et al.: “A serum based analysis of ovarian epithelial tumorigenesis”. Gynecol. Oncol., 2009, 112, 47.

[4] Nolen B., Marrangoni A., Velikokhatnaya L., Prosser D., Winans M., Gorelik E., et al.: “A serum based analysis of ovarian epithelial tumorigenesis”. Gynecol. Oncol., 2009, 112, 47.

[5] Frumovitz M., Schmeler K.M., Malpica A., Sood A.K., Gershenson D. M.: “Unmasking the complexities of mucinous ovarian carcinoma”. Gynecol. Oncol., 2010, 117, 491.

[6] Husseinzadeh N.: “Status of tumor markers in epithelial ovarian cancer has there been any progress? A review”. Gynecol. Oncol., 2011, 120, 152.

[7] Tholander B., Taube A., Lindgren A., Sjoberg O., Stendahl U., Tamsen L.: “Pretreatment serum levels of CA-125, carcinoembryonic antigen, tissue polypeptide antigen, and placental alkaline phosphatase in patients with ovarian carcinoma: influence of histological type, grade of differentiation, and clinical stage of disease”. Gynecol. Oncol., 1990, 39, 26.

[8] Tuxen M.K., Soletormos G., Dombernowsky P.: “Tumor markers in the management of patients with ovarian cancer”. Cancer Treat. Rev., 1995, 21, 215.

[9] Terzic M., Dotlic J., Likic I., Nikolic B., Brndusic N., Pilic I., et al.: “Diagnostic value of serum tumor markers evaluation for adnexal masses”. Cent. Eur. J. Med., 2014, 9, 210.

[10] Gemer O., Oustinov N., Gdalevich M., Dubnik S., Levy R., Yachnin A., et al.: “Pretreatment CA 15-3 levels do not predict disease-free survival in patients with advanced epithelial ovarian cancer”. Tu-mori, 2013, 99, 257.

[11] Sturgeon C.M., Duffy M.J., Walker G.: “The National Institute for Health and Clinical Excellence (NICE) guidelines for early detection of ovarian cancer: the pivotal role of the clinical laboratory”. Ann. Clin. Biochem., 2011, 48, 295.

[12] Moore R.G., Maclaughlan S., Bast R.C. Jr.: “Current state of biomarker development for clinical application in epithelial ovarian cancer”. Gynecol. Oncol., 2010, 116, 240.

[13] Molina R., Escudero J.M., Augé J.M., Filella X., Foj L., Torné A., et al.: “HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases”. Tumor Biol., 2011, 32, 1087.

[14] Escudero J.M., Auge J.M., 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, 1534.

[15] Van Dalen A., Favier J., Hallensleben E., Burges A., Stieber P., de Bruijn H.W., et al.: “Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up”. Eur. J. Gynaecol. Oncol., 2009, 30, 609.

[16] Moore R.G., McMeekin D.S., Brown A.K., DiSilvestro P., Miller M. C., Allard W.J., et al.: “A novel multiple marker bioassay utilizing HE4 and CA 125 for the prediction of ovarian cancer in patients with a pelvic mass”. Gynecol. Oncol., 2009, 112, 40.

[17] Huhtinen K., Suvitie P., Hiissa J., Junnila J., Huvila J., Kujari H., et al.: “Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts”. Br. J. Cancer, 2009, 100, 1315.

[18] Chudecka-Głaz A., Rzepka-Górska I., Wojciechowska I.: “Human epididymal protein 4 (HE4) is a novel biomarker and a promising prognostic factor in ovarian cancer patients”. Eur. J. Gynaecol. Oncol., 2012, 33, 382.

[19] Hamed E.O., Ahmed H., Sedeek O.B., Mohammed A.M., Abd-Alla A. A., Abdel Ghaffar H.M.: “Significance of HE4 estimation in comparison with CA125 in diagnosis of ovarian cancer and assessment of treatment response”. Diagn. Pathol., 2013, 8, 11.

[20] Langmár Z., Németh M., Vleskó G., Király M., Hornyák L., Bösze P.: “HE4 a novel promising serum marker in the diagnosis of ovarian carcinoma”. Eur. J. Gynaecol. Oncol., 2011, 32, 605.

[21] Moore R.G., Jabre-Raughley M., Brown A.K., Robison K.M., Miller M.C., Allard W.J., 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, 228.

[22] Nolen B., Velikokhatnaya L., Marrangoni A., De Geest K., Lomakin A., Bast Jr. R.C., et al.: “Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass”. Gynecol. Oncol., 2010, 117, 440.

[23] Kristjansdottir B., Levan K., Partheen K., Sundfeldt K.: “Diagnostic performance of the biomarkers HE4 and CA125 in type I and type II epithelial ovarian cancer”. Gynecol. Oncol., 2013, 131, 52.

[24] Freydanck M.K., Laubender R.P., Rack B., Schuhmacher L., Jeschke U., Scholz C.: “Two-marker combinations for preoperative discrimination of benign and malignant ovarian masses”. Anticancer Res., 2012, 32, 2003.

[25] Kelly P.J., Archbold P., Price J.H., Cardwell C., McCluggage W.G.: “Serum CA 19.9 levels are commonly elevated in primary ovarian mucinous tumours but cannot be used to predict the histological subtype”. J. J. Clin. Pathol., 2010, 63, 169.

[26] Morotti M., Menada M.V., Gillott D.J., Venturini P.L., Ferrero S.: “The preoperative diagnosis of borderline ovarian tumors: a review of current literatura”. Arch. Gynecol. Obstet., 2012, 285, 1103.

[27] Alanbay I., Aktürk E., Coksuer H., Ercan C.M., Karaşahin E., Dede M., et al.: “Comparison of tumor markers and clinicopathological features in serous and mucinous borderline ovarian tumors”. Eur. J. Gynaecol. Oncol., 2012, 33, 25.