Autoantibodies against HSF1 and CCDC155 as Biomarkers of Early-Stage, High-Grade Serous Ovarian Cancer.

Background: Tumor-directed circulating autoantibodies (AAb) are a well-established feature of many solid tumor types, and are often observed prior to clinical disease manifestation. As such, they may provide a good indicator of early disease development. We have conducted a pilot study to identify novel AAbs as markers of early-stage HGSOCs.Methods: A rare cohort of patients with early (FIGO stage Ia-c) HGSOCs for IgG, IgA, and IgM-mediated AAb reactivity using high-content protein arrays (containing 9,184 individual proteins). AAb reactivity against selected antigens was validated by ELISA in a second, independent cohort of individual patients.Results: A total of 184 antigens were differentially detected in early-stage HGSOC patients compared with all other patient groups assessed. Among the six most highly detected "early-stage" antigens, anti-IgA AAbs against HSF1 and anti-IgG AAbs CCDC155 (KASH5; nesprin 5) were significantly elevated in patients with early-stage malignancy. Receiver operating characteristic (ROC) analysis suggested that AAbs against HSF1 provided better detection of early-stage malignancy than CA125 alone. Combined measurement of anti-HSF1, anti-CCDC155, and CA125 also improved efficacy at higher sensitivity.Conclusions: The combined measurement of anti-HSF1, anti-CCDC155, and CA125 may be useful for early-stage HGSOC detection.Impact: This is the first study to specifically identify AAbs associated with early-stage HGSOC. The presence and high frequency of specific AAbs in early-stage cancer patients warrants a larger scale examination to define their value for early disease detection at primary diagnosis and/or recurrence. Cancer Epidemiol Biomarkers Prev; 27(2); 183-92. ©2017 AACR.

Clinical value of human epididymis protein 4 and the Risk of Ovarian Malignancy Algorithm in differentiating borderline pelvic tumors from epithelial ovarian cancer in early stages.

OBJECTIVE: The clinical value of human epididymis protein 4 (HE4) and the possibility of its use in the differential diagnosis in patients with benign, borderline and epithelial ovarian cancer in early International Federation of Gynaecology and Obstetrics (FIGO) stages. STUDY DESIGN: The study group consisted of 205 women, including 60 with ovarian cancer, 18 with borderline tumors, 77 with benign lesions and 50 healthy subjects. In all the patients, before the treatment and in control groups, we determined CA 125 and HE4 in serum by electrochemiluminescence on the basis of the COBAS e601 system. For comparison of two independent groups, we used the U Mann-Whitney test. The analysis of the diagnostic power of the assessed parameters has been determined using the MedCalc statistical program. The probability of disease free survival (DFS) was evaluated using the log-rank test and Cox regression model. RESULTS: Concentrations of HE4, CA 125 and Risk of Ovarian Malignancy Algorithm (ROMA) value were significantly higher in early ovarian cancer than in patients with benign (P<0.0001) and borderline tumors (P<0.002), the receiver operating characteristics (ROC) curves, demonstrated the highest diagnostic sensitivity for the ROMA score, as well post (AUC=0.817) as pre-menopausal (AUC=0.806). HE4 concentrations (P<0.021) and the value of the ROMA score (P<0.004) were significantly higher in patients with relapse than in patients in remission. There was no connection between concentrations of the studied tumor markers and DFS. CONCLUSIONS: Determination of HE4 serum concentrations has a significant clinical value, especially in patients with benign lesions and elevated CA 125 levels. The combined assessment of HE4, CA 125 and the ROMA algorithm is helpful in differentiating benign tumors and borderline pelvic tumors from epithelial ovarian cancer in early FIGO stages. Determination of HE4, CA 125 and ROMA algorithm is not helpful in differentiating patients with borderline from benign lesions.

Accuracy of serum human epididymis protein 4 in ovarian cancer diagnosis: a systematic review and meta-analysis.

OBJECTIVE: A systematic review was performed to estimate the accuracy of human epididymis protein 4 (HE4) assay in the diagnosis of ovarian tumors. METHODS: A comprehensive search of the MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google scholar; British Library) from January 1990 to April 2013 was conducted. Studies that evaluated HE4 levels for the diagnosis of ovarian tumors and compared them with paraffin-embedded sections as the diagnostic standard were included. RESULTS: Forty-five studies were analyzed, which included 10,671 women and 3946 ovarian cancer cases. The pooled sensitivity for the diagnosis of borderline tumors or ovarian cancer was 78% (95% confidence interval, 77%-79%), and the specificity was 86% (95% confidence interval, 85%-87%). Summary receiver operating characteristic curves were constructed. For malignant and borderline ovarian tumors versus benign lesions, the area under the curve was 0.916. Besides the overall analysis, stratification was performed in premenopause and postmenopause, early and late stages, and for accuracy by enzyme-linked immunosorbent assay and chemiluminescence microparticle immuno assay. CONCLUSIONS: A HE4 level is a useful preoperative test for predicting the benign or malignant nature of pelvic masses.

Extremely elevated CA-125 in benign ovarian disease due to stretch of the peritoneum.

Serum concentrations of CA-125 are rarely elevated beyond 1000 U/ml in benign conditions of the ovary in postmenopausal women. In this report, the authors present an unusual case of a 78-year-old woman with an extremely elevated CA-125 concentration of 2897 U/ml without the presence of a malignancy, ascites or pleural effusion. Imaging revealed a large intra-abdominal cystic mass with irregular solid deviations on CT scan, most likely arising from an ovary. Exploratory laparotomy was performed with suspicion of ovarian cancer but histopathological analysis revealed benign serous cystic adenofibroma. This case report highlights the diagnostic challenge of extremely increased levels of CA-125 in postmenopausal women. A possible explanation for this CA-125 elevation could be the mechanical stretch of the peritoneum.