Determination of the Reference Values of the Tumor Marker HE4 in Female Population of Canton Sarajevo

INTRODUCTION: Ovarian cancer has the highest mortality rate of all gynecological tumors and represent fifth leading cause of cancer death in women, due to the absence of early symptoms of the disease and the lack of screening tests. A new HE4 ovarian cancer biomarker was found in various studies, with different populations having quite different sensitivity and specificity values as well as reference values. The tumor marker HE4 is a useful marker for ovarian cancer detection with only minimal expression in normal ovarian tissue. HE4 is particularly promising as a marker for early detection, showing its potential in differentiating women with ovarian cancer than those with benign (nonmalignant) ovarian conditions. MATERIAL AND METHODS: Samples were taken in serum gel tubes, centrifuged and stored until analysis. A total of 300 respondents was included, of whom 188 were premenopausal women and 112 postmenopausal women. Respondents were divided into two groups by age: women aged 50-75 years and Control group of women aged 20-50 years. The HE4 assay was performed by the Immunological Test (ECLIA) for the quantitative determination of HE4 in human serum or plasma. Solid phase test, two-step reaction using immune 2HP and 3HD8 monoclonal antibodies („sandwich principle“). RESULTS: Tumor markers HE4 analysis by groups indicate that in the postmenopausal group there was 92 (82.14%) of subjects with normal tumor markers HE4 and 170 (90.43%) in the premenopausal group. The elevated values of HE4 tumor markers in the postmenopausal group were in 20 (17.86%) cases and in the premenopausal group 18 (9.57%). Statistical analysis (nonparametric method) established the upper limit of the reference value of HE4 tumor markers in premenopausal and postmenopausal women. CONCLUSION: The established reference value for the women population in Canton Sarajevo for premenopausal women is <78.6 pmol/l, and for postmenopausal women <122.5 pmol/l. We found that the values of HE4 tumor markers differ significantly in premenopausal and postmenopausal women (p=0.0391). Postmenopausal women have a higher incidence of high-value tumor markers HE4. By comparison of the reference interval of the tumor marker HE4 for the population of women from Canton Sarajevo, determined by our research, with a reference interval for the German and Asian populations, we found a significant difference between the upper limit of the reference value in postmenopausal women (p<0.05), while in premenopausal women the difference was not statistically significant (p=0.4314).