The diagnostic value of tumor marker HE4 in the differential diagnosis of gynecological diseases

Karcinom jajnika druga je najčešća maligna bolest i vodeći uzrok smrti od karcinoma u žena. CA125, do nedavno jedini tumorski biljeg u laboratorijskoj dijagnostici karcinoma jajnika, nedovoljne je dijagnostičke specifičnosti i osjetljivosti. S ciljem poboljšanja dijagnostike karcinoma jajnika ispitivano je nekoliko različitih proteina. Obećavajuće rezultate dao je sekretorni glikoprotein HE4 (eng. human epididymal protein 4). Cilj ovog rada je ispitati dijagnostičku vrijednost biljega HE4 kod bolesnica upućenih na određivanje CA125 u KBC Zagreb. Određena je vrijednost biljega HE4 i CA125 u 80 bolesnica s medijanom dobi 60 godina (21-85), elektrokemiluminiscentnom metodom na analizatoru Cobas 6000cee (ECLIA, Roche Diagnostics). Bolesnice su podijeljene u dvije skupine. Jednu su skupinu činile bolesnice s benignim oboljenjima (N=28): endometrioza, cista jajnika, dobroćudna novotvorina jajnika, lejomiom, a drugu bolesnice s malignim ginekološkim oboljenjem (N=52): zloćudna novotvorina jajnika, uterusa, cerviksa i dojke. Iako je površina ispod ROC krivulje za HE4 (AUC 0,790) veća od površine ispod ROC krivulje za CA125 (AUC 0,739), razlika u AUC nije statistički značajna (p=0,410). Kod granične vrijednosti CA125 (35 kIU/L) dobivena je osjetljivost od 92% uz specifičnost 43%, dok je za HE4 uz graničnu vrijednost od 140 pmol/L dobivena osjetljivost 53% i specifičnost od 82%. Rezultati ovog ispitivanja većinom su u skladu s aktualnim literaturnim podacima. Budući da se na ispitivanoj populaciji CA125 pokazao biljegom veće osjetljivosti, a HE4 veće specifičnosti u dijagnostici ginekoloških malignih bolesti, osobito karcinoma jajnika, optimalna dijagnostička vrijednost postigla bi se istovremenim određivanjem oba ispitivana biljega.Ovarian cancer is second most common malignancy and leading cause of cancer death in women. CA125, recently the only tumor marker in diagnostics of ovarian cancer, has insufficient diagnostic specificity and sensitivity. Several different proteins are investigated to improve diagnostics of ovarian cancer. Promising results gave secretory glycoprotein HE4. The aim of this study was to examine the diagnostic value of HE4 in patients referred to KBC Zagreb for determination of CA125. HE4 and CA125 markers were determined in 80 patients with median age 60(21-85) by electrochemiluminescent method on Cobas 6000cee (ECLIA,Roche Diagnostics). Patients were divided into two groups. Patients with benign diseases (n = 28): endometriosis, ovarian cysts, benign ovarian neoplasm, leiomyoma, and patients with malignant gynecological diseases (n = 52): malignant ovarian, uterus, cervix and breast neoplasm. Although the area under the ROC curve for HE4(AUC 0.790) was larger than the area under the ROC curve for CA125(AUC 0.739) the difference in AUCs was not statistically significant (p = 0.410). The CA125 sensitivity of 92% and specificity of 43% was obtained by cutt off 35 kIU/L while for HE4 sensitivity was 53% and specificity 82% by cutt off 140 pmol/L. Results of this study are mostly consistent with the current literature data. Since, on studied population, CA125 has been shown as a marker of greater sensitivity and HE4 greater specificity in the diagnosis of gynecological malignancies, particularly ovarian cancer, the optimal diagnostic value would be achieved by simultaneously determining both studied markers