Mouse Anti-Human HE4 monoclonal antibody, clone IN270

INTRODUCTION: The serum levels of glycoprotein human epididymis protein 4 (HE4) have been widely investigated in patients with ovarian cancer as a tumor marker to differentiate benign gynecological tumors from ovarian cancers (OC). A few studies demonstrated the promising role of HE4 in endometrial cancer (EC) too. The aim of this review is to provide an outline of published studies investigating HE4 in the diagnosis of gynecologic malignancies, focusing on its role in OC and EC. EVIDENCE ACQUISITION: We conducted a systematic review of literature from January 1952 to June 2018 on the role of HE4 in OC and EC focusing on the diagnostic power in terms of sensitivity and specificity. EVIDENCE SYNTHESIS: We identified 49 articles with an overall sample size of 12,631 patients in OC group and five studies with an overall sample size of 1221 patients in EC group. We stated that HE4 had a pooled sensitivity of 78% and specificity of 86% in the detection of borderline or malignant OC and a pooled sensitivity of 78.8% and specificity of 100% in EC diagnosis. CONCLUSIONS: This systematic review confirms the importance of HE4 in the diagnosis of epithelial ovarian cancer and its promising role in endometrial cancer (endometrioid histology).

Despite the poor prognosis of ovarian cancer and the importance of early diagnosis, there are no reliable noninvasive biomarkers for detection in the early stages of disease. Therefore, to identify novel ovarian cancer markers with potential utility in early-stage screening protocols, we have undertaken an unbiased and comprehensive analysis of gene expression in primary ovarian tumors and normal human ovarian surface epithelium (HOSE) using Serial Analysis of Gene Expression (SAGE). Specifically, we have generated SAGE libraries from three serous adenocarcinomas of the ovary and, using novel statistical tools, have compared these to SAGE data derived from two pools of normal HOSE. Significantly, in contrast to previous SAGE-based studies, our normal SAGE libraries are not derived from cultured cell lines. We have also compared our data with publicly available SAGE data obtained from primary tumors and "normal" HOSE-derived cell lines. We have thus identified several known and novel genes whose expressions are elevated in ovarian cancer. These include but are not limited to CLDN3, WFDC2, FOLR1, COL18A1, CCND1, and FLJ12988. Furthermore, we found marked differences in gene expression patterns in primary HOSE tissue compared with cultured HOSE. The use of HOSE tissue as a control for these experiments, along with hierarchical clustering analysis, identified several potentially novel biomarkers of ovarian cancer, including TACC3, CD9, GNAI2, AHCY, CCT3, and HMGA1. In summary, these data identify several genes whose elevated expressions have not been observed previously in ovarian cancer, confirm the validity of several existing markers, and provide a foundation for future studies in the understanding and management of this disease.