Four years ago, Seattle researchers identified a protein, known as Human Epididymis Protein 4 (HE4), as being highly effective in distinguishing cancer of the ovary from benign ovarian masses and cysts.   Since then additional studies have supported these initial findings, including one just published in the December 2007 edition of the journal Gynecologic Oncology.  

The only commercially available test to date, that also detects proteins elaborated by ovarian cancer, is CA-125.  It is most useful for following patients with known ovarian cancer, to assess how well patients are responding to treatment and to detect recurrence after treatment.  The problem with CA125 as a screening test  is that is it very often elevated in the presence of normal ovaries or benign ovarian cysts and tumors. In addition, CA125 is not elevated very often in early cancer of the ovary, when it is still highly curable. These two issues, render it almost useless for screening.

Just like CA125, HE4 protein breaks free from ovarian cancer cells and finds itself into the bloodstream where it can be detected.   The HE4 test, which is patented by Japanese based Fujirebio Diagnostics Inc., is  inching closer to FDA approval.  Because expression of HE4 by normal ovarian tissue or benign ovarian masses is very low, it has far better potential as a screening test than CA125.   

The latest study, headed by Dr. RG Moore, showed that  HE4 was the single best marker for Stage I, or early, cancer of the ovary.  An additional finding in the study was that combining HE4 and CA125 was better.  Statistical analysis showed that this combination had  a 76.4% sensitivity and 95% specificity, making the combination more accurate than either test alone.

HE4  is not the only bio-marker that is being investigated as an ovarian cancer screening tool. More than 30 others have been evaluated alone and in combination with CA125 by different investigators. Some of the most promising include: mesothelin, M-CSF, osteopontin, kallikrein(s), and soluble EGF receptor.  Keep an eye out for all of these in upcoming breaking news.  It is highly likely that we will have an effective screening tool combination for ovarian cancer, widely known as the “silent killer”, within the next two to three years.