A Not yet, but 4 serum protein markers may hold the key and solve the problem of finding a “needle in a haystack.”
Ovarian cancer will strike 22,000 American women this year and ultimately kill 16,000.1 This cancer tends to exhibit few early symptoms, present at an advanced stage, and have low survival rates. As Mor and colleagues note, “Despite being one tenth as common as breast cancer, epithelial ovarian cancer is 3 times more lethal.” Although modest but significant gains have been achieved through advances in surgical and medical therapy, the holy grail of ovarian cancer investigation is an effective method of early detection.
Unlike breast or prostate cancer, ovarian cancer has a very low prevalence in the general population (50/100,000). Looking for a “needle in a haystack” requires a screening tool of exceptional sensitivity and specificity. The problem: Even a screening test with 99% specificity and 100% sensitivity would yield only 1 in 21 women with a positive screen who actually has the disease.2 Ultimately, confirming the validity of a positive screen requires surgery.
How technology is spurring progress
Recent developments in molecular biology have led to an explosion of new biomarkers. Microarray technology allows the rapid screening of proteins differentially expressed in cancer versus normal cells. Each of these proteins has the potential to be used for cancer screening.
With this new technology, Mor and colleagues at Yale University identified 4 markers that, when used together, achieved a sensitivity, specificity, and positive predictive value of 95%, with a negative predictive value of 94%. The markers are leptin, prolactin, osteopontin, and insulin-like growth factor-II. They successfully detected 23 of 24 patients with stage I and II disease. When compared with screening strategies based on proteomic patterns generated by mass spectroscopy, these markers are far less complex and expensive.3
Ovarian cancer screening strategies pursued over the past 20 years include the use of serum tumor markers such as CA 125, imaging modalities such as transvaginal sonography, or both. To date, no single test or combination of tests has achieved the high standards required for screening, even among high-risk populations. However, this may soon change.
The bottom line
Unfortunately, these markers do not yet meet the stringent requirements for population-based screening. To do so, they must be validated in a much larger population of patients and must have sensitivity and specificity well above current levels. When compared to CA 125 alone, however, they represent a remarkable improvement.
In the future, the authors predict the markers should “improve our ability to accurately detect premalignant change or early stage ovarian cancer in asymptomatic women at increased risk.”
The commentators report no financial relationships relevant to this article.