Many different tumour associated antigens have been described and investigated. The most commonly used markers circulating in the blood are neuron specific enolase (NSE), carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), squamous cell carcinoma antigen (SCC), cancer antigen CA 125 (CA 125) and tissue polypeptide antigen (TPA.)
NSE is a glycolytic neurospecific isoenzyme of enolase. It consists of two almost identical polypeptide chains, each with a molecular weight of 39 kD. It is produced in central and peripheral neurons and malignant tumours of neuroectodermal origin (e.g. SCLC, neuroblastomas, intestinal carcinoid). Furthermore, as NSE is also found in erythrocytes, plasma cells and platelets it may be released into serum if separation from red cells does not occur within 60 minutes of venepuncture.
CEA is a glycoprotein of molecular weight of ~180 kD. It is one of the carcinofetal antigens produced during embryonal and fetal development. CEA was one of the first tumour markers to be described, and has relatively high sensitivity for many advanced adenocarcinomas (primarily colon, but also breast, stomach and lung cancer). Sensitivity of CEA measurement is greatest, and serum CEA concentrations are highest, in adenocarcinoma and large cell lung cancer.
SCC is a 48 kD protein with strong homology to the serpin family of protease inhibitors. Serum measurements of SCC have been used in squamous cell carcinomas of the cervix, oesophagus, head, neck and lung. One of the most important applications of SCC measurements in lung cancer is as an aid to histological diagnosis.
CA125 (MW ~200 kD) is the second hybridoma-defined tumour marker. It is a differentiation antigen that arises in fetal tissue from coelomic epithelial derivatives. Serum measurements are mainly used in serous ovarian carcinomas but are sometimes used in breast and lung cancer.
TPA is, like CEA, one of the oldest tumour markers. TPA assays measure a mixture of cytokeratins 8, 18 and 19. Since the development of monoclonal antibody technology, antibodies to cytokeratins and other intermediate filaments of the cell (e.g. vimentin, desmin) have been used in histopathology for the differentiation and classification of pathological tissue. In contrast to cytokeratins themselves, fragments of intermediate filaments are soluble in serum, where they can be detected as aggregates with the aid of monoclonal antibodies.
CYFRA 21.1 is a relatively new tumour marker test which uses two specific monoclonal antibodies against a cytokeratin 19 fragment. Histopathological studies demonstrate that cytokeratin 19 is abundant in carcinomas of the lung. CYFRA 21-1 is especially suitable for NSCLC as it is the most sensitive tumour marker in these histologies including squamous tumours. Since CYFRA 21.1 determines only fragments of cytokeratin 19, the test shows a higher specificity than TPA, which determines a mixture of cytokeratins 8, 18 and 19.