Gastric carcinogenesis: when is the point of no return?

Abstract

Over the past few years we have begun to accept a concept of carcinogenesis in which a series of mutations in important genes leads to the development of the fully fledged invasive phenotype of cancer. At the same time we have attempted, not always with success, to correlate these mutational events with the morphological pre-neoplastic lesions which have long been recognized Thus, in the colon, we subscribe to the view that most carcinomas arise from a pre-existing non-invasive lesion, the adenoma. Later research showed that the adenoma itself had a precursor lesion - the so-called aberrant crypt focus. It is now appreciated that the mutations which are associated with aberrant crypt foci and adenomas in the colon are heterogeneous, and that while we still accept the concept of sequential, mutation events leading to carcinoma, we accept that the order and timing of these events may vary, and that the mutational events themselves may be different in any given lesion. Even though knowledge of the molecular events leading to the development of carcinoma of the colon is quite extensive, it would be difficult to say, with any degree of confidence, where the point of no return in this pathway lies. There have been studies in which adenomas have been followed, without intervention, for up to 14 years before an invasive event has occurred¹, and so it might be considered appropriate that the adenoma be considered the point of no return. But I shall argue that a point of no return, within the concept of carcinogenesis, is a difficult one to accept, certainly within the colon, and also, as we shall see, in the gastric mucosa.