Classification of tumor markers.

Since the discovery of the first tumor markers more than a century ago (Bence-Jones proteins), a vast array of molecules have been described as being associated with cancer. These are generally naturally occurring biomolecules with the exception of neo-antigens expressed in certain tumors induced by viruses. Tumor markers can be broadly classified into tumor specific antigens and tumor-associated markers. Most tumor markers were often heralded as highly tumor specific but subsequent studies demonstrated their presence in normal tissues of the adult or in various stages of ontogeny. As a result, very few tumor-specific antigens can be recognized. The idiotypes of immunoglobulins of B cell tumors and certain neo-antigens of virus induced tumors are two examples that are strictly tumor specific. The vast majority of tumor markers are in reality tumor-associated antigens and can be classified into two types based on their size. The low-molecular weight tumor markers (approximately < 1000 Daltons) include some nucleosides, lipid associated sialic acid, polyamines, pseudouridine, pigment derivatives, and other metabolites. The macromolecular tumor antigens are the most important sub-type useful in the clinical management of cancer patients. The large cancer antigens are either enzymes, growth factors, hormones, receptors, biological response modifiers, oncogenes and their products, or glycoconjugates which include glycoproteins and glycolipids. Collectively all the commercial tumor marker assays available to the oncologist for cancer patient management amount to an annual sales of > $1 billion world wide. The demonstrated clinical usefulness and commercial success of tumor markers have continued to fuel exciting research into the discovery and novel uses of new analytes.