Early Detection Of Ovarian Cancer

The majority of women with ovarian cancer are diagnosed with advanced stage disease. One of the most imperative issues in ovarian cancer is early detection. Biomarkers that allow cancer detection at stage I, a time when the disease is amenable to surgical and chemotherapeutic cure in over 90% of patients, can dramatically alter the horizon for women with this disease.

Few cancers are characterized by a single reliable biomarker; thus, the challenge in identification of an OCS tool is how and what information to combine to engineer the most sensitive and specific and reliable discriminant of disease. The field of proteomics has brought new technology to detect ovarian cancer and offers a series of new directions that may bear fruit.

The group represented by Dr Elise Kohn hypothesized that circulating blood is exposed to disease even when organ-confined, and, therefore, could harbor occult information regarding that disease. This is not a novel hypothesis assuming that prostate-specific antigen (PSA) can be elevated in organ-limited prostate cancer and elevated b-HCG (human chorionic gonadotrophin) is a marker of pregnancy, an organconfined process. The twist on the hypothesis is that  the proteins in the circulating blood may be iterated into patterns that provide diagnostic information in the absence of specific identification. Proteins, the effector organs of genomics and transcriptomics, are often secreted or released into the local microenvironment where they may end up in the circulating blood.

Application of micro mass spectroscopy coupled with complex bioinformatic techniques to samples of blood from affected and unaffected patients has shown promise for identification of discriminating protein signature patterns in the blood of organ-confined disease for ovarian cancer and other solid tumors. Surfaceenhanced laser desorption and ionization (SELDI) or matrix-assisted laser desorption and ionization (MALDI) with time of flight (TOF) detection is a mass spectroscopy approach that allow us to ‘see’ selected components of the low molecular weight proteome, a heretofore untapped information reserve. Simple serum samples of less than 10 ml have been used routinely in the SELDI-TOF system.

These results reported by Kohn and colleagues coupled with preliminary application of this technology by other several groups have shown it to be promising as a new biomarker tool. Demonstration of a sensitivity and specificity both 99—100% indicate that this approach may have the power to detect early ovarian cancer signs in the range required for a realistic biomarker.

Large-scale prospective and blinded studies are required to determine the robustness of these early findings and to form the basis for its application in prospective screening trials. Proteomics is a promising direction for clinical and scientific advancement in our understanding and diagnosis of ovarian and other gynecologic cancers.

Last updated Nov 26/06