Ovarian cancer is the most lethal gynaecological malignancy, with the majority of cases diagnosed with metastatic disease. If there are tumour specific biomarkers present in plasma at an early stage of the disease, these might contribute to an earlier detection and therapy and potentially a more positive outcome. Proteins specific for the tumour tissue can be expected to be found in high concentrations in the interstitial fluid compared to plasma, suggesting that the tumour interstitial fluid may be a valuable source for identification of tumour specific proteins. Thus, we have isolated the tumour interstitial fluid from human ovarian cancer tissue by centrifugation, i.e. by exposing tumour specimens to 38 g as described by Wiig et al. 2003. To allow a better separation and identification of low abundant proteins the fluid was further fractionated by immunodepletion and reversed phase chromatography. This fluid was compared to plasma from the patients and healthy women with respect to protein composition in one-dimensional liquid chromatography coupled with tandem mass spectrometry. Eighty-seven and 91 proteins were identified by at least two peptides in control plasma and patient plasma respectively, and 232 proteins were identified by at least two peptides in tumour interstitial fluid. Our experiments show that tumour interstitial fluid is a rich source for tumour specific proteins, and some of these may be candidates for the use in ovarian cancer diagnostics.

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Wiig, H., Aukland, K. & Tenstad, O. 2003. Am J Physiol Heart Circ Physiol 284, H416-H424.