The Lancet

Volume 359, Number 9306 * Founded 1823 * Published Weekly * Saturday 16 February 2002 * pages 572-577 *

Use of Proteomic Patterns in

Serum to Identify Ovarian Cancer

Petricoin EF*, Ardekani AM, Hitt B+, Levine P+, Steinberg S*, Mills G,

Simone CB#, Fishman D, Kohn E*, Liotta LA.*

Sir In the year 2002 about 24,000 American women will be diagnosed with ovarian cancer and about 14,000 will die from it. There has been no effective method of early detection of ovarian cancer and consequently the great majority of patients with newly diagnosed ovarian cancer are detected in late stages. New technologies are critically needed.

Certain abnormal proteins (proteomic) may be secreted in unique patterns into the blood stream from pathological changes within an organ. To detect these unique abnormal protein patterns, a bioinformatics tool was developed to distinguish cancer from non-cancer diseases of the ovary.

First, serum from each patient with an ovarian problem (cancer or non-cancer), is placed on a special surface that attracts specific proteins, in this case, hydrophobic proteins. Repeated washings with special chemicals remove unwanted proteins. Then a laser beam is used to hurl the remainder proteins from the surface into a chamber separating the lighter weight proteins from the heavier proteins. Hence, a unique Proteomic Pattern of different weighted proteins is created after Laser treatment for each serum specimen: light, moderate, and heavy weight. This technique is known as Surface Enhanced Laser Desorption and Ionization (SELDI).


Wash Laser

A large number of unique proteomic patterns may occur. Therefore, a bioinformatics tool, a special software program, was developed to recognize patterns and match subsequent test serum samples with known patterns from either cancer or non-cancer patient proteomic patterns. For example, let's say that the serum used in the diagram was from a patient with ovarian cancer. Then proteomic patterns from other patients that are identical or very similar could suggest a cancer as well.

Findings: This new technology accurately identified all 50 ovarian cancer cases that included 18 stage I cases. Of the 66 cases of non-cancer disease, 63 were recognized as non- cancer. This yielded a sensitivity of 100 percent, specificity of 95 percent, and a positive predictive value of 94 percent compared with a positive predictive value of only 34 percent for the blood test currently used to detect ovarian cancer, the CA-125 test.

Interpretation: Serum proteomic pattern profiling may constitute a sensitive and specific and specific tool for early ovarian cancer identification. These findings warrant prospective clinical application of this technology.

How You Can Help: If you have a newly diagnosed and untreated disease of the ovary (ies), cancer or non-cancer, please call 609- 896-2646.

*National Cancer Institute, NIH investigators +Correlogic Systems

#Simone Protective Cancer Institute investigator