Comparison of Serum Human Epididymis Protein 4 with Cancer Antigen 125 as a Tumor Marker in Patients with Malignant and Nonmalignant Diseases

Abstract

BACKGROUND Human epididymis protein 4 (HE4), a precursor of human epididymis protein, has been proposed as a tumor marker for ovarian cancer. We evaluated HE4 in comparison with cancer antigen 125 (CA 125) in healthy individuals and in patients with benign and malignant diseases. METHODS CA 125 and HE4 serum concentrations were determined in 101 healthy individuals, 535 patients with benign pathologies (292 with benign gynecologic diseases) and 423 patients with malignant diseases (127 with ovarian cancers). CA 125 and HE4 cutoffs were 35 kU/L and 140 pmol/L, respectively. RESULTS HE4 and CA 125 results were abnormal in 1.1% and 9.9% of healthy individuals and in 12.3% and 37% of patients with benign diseases, respectively. Renal failure was the most common cause of increased HE4 in patients with benign disease, who had significantly higher HE4 concentrations (P = 0.001) than patients with other benign diseases. HE4 showed a higher specificity than CA 125 in patients with benign gynecologic diseases, with abnormal concentrations in 1.3% and 33.2% of the patients, respectively. HE-4 concentrations were abnormal primarily in gynecologic cancer and lung cancer. By contrast, CA 125 was increased in many different nonovarian malignancies, including nonepithelial tumors. A significantly higher area under the ROC curve was obtained with HE4 than with CA 125 for differentiating benign from malignant diseases (0.755 vs 0.643) and in the differential diagnosis of gynecologic diseases (0.874 vs 0.722). CONCLUSIONS HE4 has significantly higher diagnostic specificity than CA 125, and the combination of CA 125 and HE4 improved the detection of ovarian cancer in all stages and histological types.

Human epididymis protein 4 (HE4) in benign and malignant diseases

“…This result is similar to other biomarkers like ProGRP or SCCA and was also described recently by Escudero 2011 for HE4 (12) . As a consequence, HE4 should not be used in patients with renal insuffi ciency or patients with abnormal serum creatinine levels.…”

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

“…Primary hepatocellular carcinoma tissues were negative for HE4 expression by immunohistochemistry standard [26]. Escudero and coworkers measured serum HE4 concentrations in 81 cases of patients with liver diseases including 15 cases of hepatitis and 66 cases of liver cirrhosis [89]. They observed a marginal increase in serum HE4 in merely 2% of patients with liver diseases without effusions.…”

“…High HE4 expression is observed in the distal convoluted tubules of the kidney and low expression in the proximal convoluted tubules [56,89]. Data on HE4 tissue expression in benign urinary tumor are sparse.…”

Human Epididymis Protein 4 Reference Intervals in a Multiethnic Asian Women Population

“…The survival rate at this advanced stage is <20% despite aggressive surgery and chemotherapy (Hellstrom et al, 2003). Ovarian cancer accounts for nearly 4% of all cancers among women and has been ranked as the fifth most common cause of cancer death in women (Escudero et al, 2011). In Malaysia, ovarian cancer was ranked as the fourth most common cancer in (Malaysian Cancer Statistics, 2007).…”

“…Cancer antigen 125 (CA125) has been the tumor marker of choice for ovarian cancer. However, the diagnostic sensitivity is low when it is related to tumor stage, (abnormal levels were seen in 50% of stage 1 patients and 80-90% in stage III-IV) (Escudero et al, 2011) and 20% of epithelial ovarian cancers do not expressed CA125 (Bast and Badgwell, 2005).…”