Tumour markers in oncology: past, present and future

Historically, tumour markers are substances selectively released by tumour cells in the blood stream so that they can be detected in the serum or other body fluids for clinical monitoring of various malignancies. The term is now extended to cell or tissue characteristics, such as cytogenetic markers, oncogenes or abnormally expressed proteins with various biological functions (enzymes, receptors, etc.), which help characterize the tumour type and constitute specific biological targets for new drugs. Serum markers can be classified in three main categories: (i) oncofetal antigens which are normally expressed only during fetal life, (ii) carbohydrate antigens as part of glycolipids or glycolipoproteins (mucins) and (iii) miscellaneous, including tissue specific enzymes, cytoskeletal proteins, etc. Most carbohydrate antigens which are useful in serum diagnosis of human cancers show tumour type-specific aberrant glycosylation, with O instead of N linkage to protein moieties. Despite a huge progression in analytical performances with immunoassays, and because of still insufficient biological sensitivity and specificity, serum assays of tumour markers are not effective in mass screening, their usefulness being restricted to the follow-up of diagnosed patients. Selective expression of specific antigens allows in vivo detection of occult tumour masses (immunoscintigraphy) and immunotargetting of drugs as therapy. Cell and tissue markers comprise markers of transformation (molecular genetics, oncogenes and anti-oncogenes, etc.), differentiation (hormone receptors, etc.), proliferation (growth factors, Ki67, etc.) and metastatic potential (proteases, etc.). Although masking the functional aspects of many of these markers, as for hormone or growth factor receptors, immunoanalytical methods, specially immunohistochemistry, are rapidly expanding in clinical oncology as tools for diagnosis, prognosis and, promisingly, treatment adjustment.