An ovarian cancer malignancy risk index composed of HE4, CA125, ultrasonographic score, and menopausal status: use in differentiation of ovarian cancers and benign lesions

Abstract

A case-control study included 83 ovarian cancer patients, 76 patients with benign ovarian tumors, and 79 healthy control subjects in the control group. Objective of the study is to analyze biomarker concentrations included in the two novel ovarian tumor differential diagnostic tests (risk of ovarian malignancy algorithm and OVA1) approved by food and drug administration in patients with ovarian tumors and to establish a new ovarian cancer risk assessment algorithm in conjunction with ultrasound score and menopausal status. Ovarian cancer diagnostic tests, developed in the training setting, were evaluated in the independent validation settings of Asian Pacific ovarian cancer biomarker research group study population and Denmark Pelvic Mass project population. Results show that mean serum concentrations of cancer antigen 125 (CA125), human epididymis secretory protein 4 (HE4), and beta-2-microglobulin were upregulated, but apolipoprotein A1, transferrin, and transthyretin were downregulated among ovarian cancer patients. When only one biomarker was introduced in the logistic regression analysis, together with ultrasonographic score and menopausal status, HE4 (area under the curve (AUC) = 0.930; 95 % confidence interval (CI) 0.891-0.969) was more accurate than CA125 (AUC = 0.902; 95 % CI 0.855-0.949) in ovarian cancer diagnostic, but when both biomarkers were included in the logistic regression analyses, ovarian cancer diagnostic accuracy was increased (AUC = 0.939; 95 % CI 0.902-0.977). In conclusions, human epididymis secretory protein 4 and CA125 in combination with ultrasonographic features and menopausal status has high accuracy in ovarian tumor differentiation.

Human epididymis protein 4 (HE4) in laboratory medicine and an algorithm in renal disorders

“…In a comprehensive clinical study, HE4 levels were above the reference range only in around 1% of cases versus 33% for CA125 in those women with endometriosis [9]. Hence, HE4 has a substantial diagnostic power in the differentiation of endometriosis from ovarian or endometrial cancer, which was approved by several studies [9,11,[23][24][25]31,41]. In liver cirrhosis, HE4 levels could be as high as 2000 pmol/L, similarly as could be seen in the advanced stage of EOC [11].…”

“…The first such approach has long been suggested by Jacobs and coworkers [30] by combining the values of CA125 with ultrasound and menopausal status, resulting in the creation of the risk of malignancy index (RMI). This strategy was further developed when HE4, in combination with CA125 plus ultrasonographic features and menopausal status, demonstrated high accuracy in ovarian tumor differentiation [31]. Similarly to RMI, another multiple marker bioassay, the risk of ovarian malignancy (ROMA) was described utilizing the HE4 and CA125 values for the prediction of epithelial ovarian pelvic masses [22,32].…”

HE4 as a Serum Biomarker for ROMA Prediction and Prognosis of Epithelial Ovarian Cancer

“…Overall, the 5-year survival rate associated with ovarian cancer is less than 30% (Andersen et al, 2008). Therefore, it is crucial to establish more sensitive and specific diagnostic tests and algorithms for the prediction of ovarian cancer at an early stage (Anton et al, 2012;Macuks et al, 2012). Moreover, optimization of treatment strategies and therapy-monitoring policies may have a substantial impact on patient survival.…”

Panels of protein biomarkers and non-protein markers in the diagnosis of the ovarian cancer

“…Za pomocą specjalnego algorytmu oblicza się wynik testu podawany w postaci liczbowej (0-10), który wskazuje, czy mamy do czynienia z guzem łagodnym czy złośli-wym. Należy zwrócić uwagę, że wyniki wskazujące na wysokie ryzyko różnią się dla kobiet w okresie przedmenopauzalnym (≥ 5,0) oraz po menopauzie (≥ 4,4) [6,10].…”