Prognostic factors in gastric cancer

BACKGROUND: Despite gastric cancer being common, its prognosis has not been improved significantly in recent years. Now, greater insight has been gained into the biological properties of tumour cells, how they become malignant and what mechanisms they may use to invade and metastasize. This involves tumour-associated protease systems, loss or mutation of adhesion molecules and changes in genetics. The view of gastric cancer is changing: it is not only a solid tumour but also exhibits a minimal residual disease component even in the early stages of disease. Such biological tumour characteristics may provide new prognostic factors and also potential new therapeutic options. METHODS: This is an update of prognostic factors in gastric cancer, emphasizing new biological features, some of which have been investigated by this group over the past few years. Current results are discussed in the light of 212 references obtained from the Medline database from 1979 to 1997. RESULTS: There is high probability that some of the factors reviewed, such as c-erbB-2, individual course and phenotyping of disseminated tumour cells will become significant new prognostic variables. This is true also, to a lesser extent, of cathepsin D, matrix metalloproteinase 2 combined with activators or tissue inhibitor of metalloproteinases 2, CD44, E-cadherin, p53 and cripto. Plasminogen activator inhibitor 1 (PAI-1), a member of the urokinase-type plasminogen activator (uPA) system, can already be defined as an established new prognostic factor in gastric cancer. CONCLUSION: PAI-1 should be considered prognostically in addition to established tumour classifications. Moreover, the uPA system is a target for future therapeutic concepts. Further analysis of factors describing tumour biology should lead to new, functionally orientated, tumour classifications in gastric cancer.