Usefulness of determining CA 125 and HE4 serum concentration in diagnosis of ovarian cancer
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Beskidzkie Centrum Onkologii – Szpital Miejski im. Jana Pawła II w Bielsku-Białej
Izabela Agnieszka Gumółka   

Beskidzkie Centrum Onkologii Szpital Miejski im. Jana Pawła II w Bielsku-Białej, ul. Wyzwolenia 18, 43-300 Bielsko-Biała, tel. + 48 508 363 198, fax. +48 334 984 056
Ann. Acad. Med. Siles. 2015;69:138–149
Ovarian cancer is a malignant tumor that is the most common cause of death among women with abnormalities of the reproductive organs. CA125 plays a key role in the diagnosis of ovarian cancer. However, according to recent reports, potentially new markers may be HE4 and ROMA. The aim of study was to assess the clinical usefulness of marker concentrations in the serum of women with ovarian cancer and ROMA determination, as well as to compare the results of those obtained from patients with endometrial cancer and from healthy women.

Materials and methods:
The study was conducted in the Beskid Oncology Centre in Bielsko-Biala, in the following groups of women: control group – healthy women, I research group – women with ovarian cancer, II research group – women with non-malignant gynecological diseases and III research group – women with endometrial cancer. In order to determine the concentrations of the markers, the immunological method with electrochemiluminescence technology was applied.

A statistically significant difference between the marker concentrations and specified value of ROMA in the groups of healthy women and of those with ovarian cancer (p < 0.001) and with non-malignant gynecological disorders (CA125 p < 0.001, HE4 p = 0.034; ROMA p = 0.012) was demonstrated. The ROC curve analysis showed that determining the markers’total concentration and determining ROMA significantly improves the diagnostic value of the test as compared to single-marker determination (AUC:CA125 69%; HE4 85%; ROMA 90%).

Simultaneous measurements of CA125 and HE4 concentrations as well as determining ROMA for the differential diagnosis of pelvic tumors and gynecological cancers (ovarian, endometrial cancer) were proven useful.

Stempczyńska J., Potemski P. Nowotwory jajnika. W: Onkologia-podręcznik dla studentów i lekarzy. Red. R. Kordek. Medical Press, Gdańsk 2003, 190–195.
Partheen K., Kristjansdottir B., Sundfetdt K. Evaluation of ovarian cancer biomarkers HE4 and CA–125 in women presenting with a suspicious cystic ovarian mass. J. Gynecol. Oncol. 2011; 22: 244–252.
Van Gorp T., Veldman J., Van Calster B. et al. Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses. Eur. J. Cancer 2012; 48: 1649–1656.
Havrilesky L.J., Whitehead C.M., Rubatt J.M. et al. Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol. Oncol. 2008; 110: 374–382.
Galgano M.T., Hampton G.M., Frierson H.F. Jr. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod. Pathol. 2006; 19: 847–853.
Kurman R.J., Hedrick Ellenson L., Ronnett B.M. Blaustein’s pathology of the female genital tract. Springer Sixth Edition. London 2011, 684–685.
Webb P.M., Purdie D.M., Grover S., Jordan S., Dick M.L., Green A.C. Symptoms and diagnosis of borderline, elary and advanced epithelial ovarian cancer. Gynecol. Oncol. 2004; 92: 232–239.
Hellström I., Raycraft J., Hayden-Ledbetter M. et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 2003; 63: 3695–3700.
Dahl Steffensen K., Waldstrøm M., Brandslund I., Jakobsen A. Prognostic impact of prechemotherapy serum levels of HER2, CA125, and HE4 in ovarian cancer patients. Int. J. Gynecol. Cancer 2011; 21: 1040–1047.
Lu R., Sun X., Xiao R., Zhou L., Gao X., Guo L. Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility. Biochem. Biophys. Res. Commun. 2012; 419: 274–280.
Zou S.L., Chang X.H., Ye X. et al. Effect of human epididymis protein 4 gene silencing on the malignant phenotype in ovarian cancer. Chin. Med. J. 2011; 124: 3133–3140.
Bast R.C., Feeney M., Lazarus H., Nadler L.M., Colvin R.B., Knapp R.C. Reactivity of a monoclonal antibody with human ovarian carcinoma. J. Clin. Invest. 1982; 5(68): 1331–1337.
Meyer T., Rustin G.J.S. Role of tumour markers in monitoring epithelial ovarian cancer. Br. J. Cancer 2000; 82: 1535–1538.
Rufford B., Menon U., Jacobs I. Screening for familial ovarian cancer. W: Familial breast and ovarian cancer. Genetics, screening and management. Ed. Morrison P.J., Hodgson S.V., Haites N.E. Cambridge University Press, Combridge 2002, 220–233.
Bagan P., Berna P., Assouad J., Hupertan V., Le Pimpec Barthes F., Riquet M. Value of cancer antigen 125 for diagnosis of pleural endometriosis in females with recurrent pneumothorax. Eur. Respir. J. 2008; 1: 140–142.
Amaral V.F., Ferriani R.A., Sá M.F. et al. Positive correlation between serum and peritoneal fluid CA-125 levels in women with pelvic endometriosis. Sao Paulo Med. J. 2006; 124: 223–227.
Sarandakou A., Protonotariou E., Rizos D. Tumor markers in biological fluids associated with pregnancy. Crit. Rev. Clin. Lab. Sci. 2007; 2: 151–178.
Jemal A., Tiwari R., Murray T. et al. Cancer statistics, 2004. CA Cancer J. Clin. 2004; 54: 8–29.
Pike M., Pearce C.L., Wu A.H. Prevention of cancers of the breast, endometrium and ovary. Oncogene 2004; 23: 6379–6391.
Patterson S.D., Aebersold R.H. Proteomics: the first decade and beyond. Nat. Genet. 2003; Suppl. 33: 311–323.
Molina R., Escudero J.M., Augé J.M. et al. HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases. Tumour Biol. 2011; 32: 1087–1095.
Holcomb K., Vucetic Z., Miller M.C., Knapp R.C. Human epididymis protein 4 offers superior specificity in the differentiation of benign and malignant adnexal masses in premenopausal women. Am. J. Obstet Gynecol. 2011; 205: 358.e1-6.
Nolen B., Velikokhatnaya L., Marrangoni A. et al. Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. Gynecol. Oncol. 2010; 117: 440–445.
Kim Y.M., Whang D.H., Park J. et al. Evaluation of the accuracy of serum human epididymis protein 4 in combination with CA125 for detecting ovarian cancer: a prospective case-control study in a Korean population. Clin. Chem. Lab. Med. 2011; 49: 527–534.
Andersen M.R., Goff B.A., Lowe K.A. et al. Use of a Symptom Index, CA125, and HE4 to predict ovarian cancer. Gynecol. Oncol. 2010; 116: 378–383.
Kulpa J.K., Wójcik E., Rychlik U., Sobolewska K., Tarapacz J. HE4 i CA 125 – porównanie metod oznaczeń. Diagn. Lab. 2012; 48: 41–49.
Rein B.J., Gupta S., Dada R., Safi J., Michener C., Agarwal A. Potential markers for detection and monitoring of ovarian cancer. J. Oncol. 2011; 2011:U75983. doi: 10.1155/2011/475983.
Shah C.A., Lowe K.A., Paley P. et al. Influence of ovarian cancer risk status on the diagnostics performance of the serum biomarkers mesothelin, HE4, and CA 125. Cancer Epidemiol. Biomarkers Prev 2009; 18: 1365–1372.
Anastasi E., Marchei G.G., Viggiani V., Gennarini G., Frati L., Reale M.G. HE4: a new potential early biomarker for the recurrence of ovarian cancer. Tumour Biol. 2010; 31(9): 113–119.
Halila H., Stenman W.H., Sepälä M. Ovarian cancer antigen CA 125 levels in pelvic inflammatory disease and pregnancy. Cancer 1986; 57: 1327–1329.
Urban N., Thorpe J., Karlan B.Y. et al. 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: 2087–2094.
Bignotti E., Ragnoli M., Zanotti L. et al. Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients. Br. J. Cancer 2011; 104: 1418–1425.
Kalogera E., Scholler N., Powless C. et al. Correlation of serum HE4 with tumor size and myometrial invasion in endometrial cancer. Gynecol. Oncol. 2012; 124: 270–275.
Hynninen J., Auranen A., Dean K. et al. Serum HE4 profile during primary chemotherapy of epithelial ovarian cancer. Int. J. Gynecol. Cancer 2011; 21: 1573–1578.