Ovarian and Endometrial Cancer is the fourth or fifth most common cause of cancer-related deaths among women worldwide and is responsible for 5% of all cancer deaths in women. The high death rate is mostly attributable to its late detection. Earlier detection is essential for improved survival.
CA125 is, to date, the best known test for ovarian cancer diagnosis, and is the serum marker most widely used to monitor therapeutic response and to detect disease, or disease recurrence, for epithelial ovarian cancer. Its recognised limitations have prompted the need to develop biomarkers with better sensitivity for early stage diagnosis, with the ability to differentiate women with ovarian cancer from those with benign ovarian conditions. CA125 has a high false positive rate among women with benign gynaecological conditions such as endometriosis. Approximately 20% of ovarian cancers lack expression of CA125, and levels are not increased in nearly 40 – 50% of early stage ovarian cancers. The diagnostic value of CA-125 is compromised by its high false-positive rate.
HE4 is a new marker for ovarian carcinoma, which is over-expressed in patients with ovarian and some other cancers. When combined with CA125, HE4 raises the potential to discriminate benign from cancerous ovarian masses and has the strongest correlation with endometrial cancer of all markers tested to date. HE4 is consistently expressed in patients with ovarian cancer and has demonstrated an increased sensitivity and specificity over that of CA125 alone.
High HE4 with High CA125 would suggest ovarian cancer whereas an elevated CA125 without an associated elevated HE4 indicate benign conditions. A raised HE4 and normal CA125 would suggest the presence of either ovarian or possibly other type of cancer (e.g. endometrial). It is promising as a marker for early detection by differentiating women with ovarian cancer from women with benign ovarian conditions
A Risk of Ovarian Malignancy Algorithm (ROMA) classifies patients as being at low or high risk for malignant disease using both the CA125 and HE4 results, and a woman’s menopausal status. This risk is reported with results for both CA125 and HE4. ROMA calculates a risk of finding ovarian cancer during surgery. ROMA classifies patients as being at low or high risk for malignant disease.