Marker of Early Ovarian Cancer Identified

Women with elevated levels of a substance called human epididymis protein (HE4) in their blood are more likely to have ovarian cancer. This finding will aid in the development of test for early detection of the disease dubbed the ‘silent killer,' for which there is no adequate screening test.

Currently, the gold standard for monitoring ovarian cancer is a test that measures levels of the marker cancer antigen- (CA)-125 in blood. CA-125 is a protein that is more prevalent in ovarian cancer cells than in other cells. This protein enters the blood stream and can be measured by a blood test. There are two CA-125 tests, a first- and second-generation test. The second-generation test is now more widely used and is generally more accurate. The test is limited in detecting all types of ovarian cancer, prompting scientists to seek additional biomarkers that offer higher sensitivity and can be indicative of the disease to complement CA-125.

In a study led by Dr. Richard Moore, assistant professor in the Program for Women's Oncology at Women and Infants Hospital, Brown University (Providence, RI, USA), nine potential biomarkers in 259 patients with pelvic masses were evaluated. The team measured levels of each biomarker within the women's blood and then compared the results with biopsies of their tumors. With 72.9% sensitivity and 95 % specificity, HE4 was the most effective biomarker for detecting ovarian cancer. When CA-125 was added, the result was even better, and sensitivity for detecting the disease increased to 76.4%.

HE4 is a secreted glycoprotein known to be overexpressed by serous and endometrioid ovarian carcinomas. Dr. Moore's study noted that HE4 is the best single marker for stage I disease. Seventy to 75% of ovarian cancers are diagnosed at a late stage when the five-year overall survival rate may only reach up to 50%. However, in women diagnosed with stage I disease, the probability of a cure approaches 90-95%.

"Ovarian cancer is often difficult to diagnose because symptoms are often recognized in the late stages of the disease when ovarian cancer is fundamentally incurable,” said Dr. Moore. "Our results show testing women suspected of ovarian cancer for both CA-125 and HE4 could possibly lead to a screening and diagnostic tool. This is exciting news, particularly for women in the earliest stages of the disease when it is most treatable.”

"This is an encouraging development not only for ovarian cancer patients, but for all women with ovarian cysts as it can be challenging to distinguish malignant tumors from benign ones with current methods,” said Dr. Olle Nilsson, vice president and CSO of Fujirebio Diagnostics (Malvern, PA, USA), the developers of the CA-125 test. "A combination of tests could help clinicians better define ovarian cysts so they can determine the most appropriate treatment regimen for their patients.”

The results of the study were published online in the December 3, 2007 Journal of Gynecologic Oncology.

Fujirebio Diagnostics has developed a manual test for HE4 and will be developing automated formats of the test for Fujirebio instruments. The company plans to submit to the U.S. Food and Drug Administration (FDA; Rockville, MD, USA), for regulatory clearance of the HE4 test later this year.


Related Links:
Women and Infants Hospital, Brown University
Fujirebio Diagnostics
U.S. Food and Drug Administration