Cell proliferation, cell death, E-cadherin, metalloproteinase expression and angiogenesis in gastric cancer precursors and early cancer of the intestinal type

The aim of this study was to analyse the morphological, kinetic and molecul ar characteristics of low-grade (LGD) and high-grade dysplasias (HDG) in co mparison with intestinal metaplasia type III (IM III) and normal mucosa (NM ) as well as with early gastric cancer of the intestinal type (EGC). Based on this it was verified whether these categories are distinct, progressive proliferative steps from IM III to LGD, HGD and EGG, according to Correa's sequence of events. The morphology, mitotic index (MI), and the apoptotic i ndex (AI) were assessed. The E-cadherin expression (E-Cad), matrix-metallop roteinase activity (MMP2), and the number of microvessels (NV) were also ev aluated. Among the categories, MI increases from NM, to IM III and LGD, and fi om LGD to HGD and EGG, while AI continues to increase also from HGD to EGG. E-Cad decreases from NM to EGG, although not significantly from LGD to HGD; MMP2 is significantly more expressed only in EGG. Three groups are ob tained by means of cluster analysis. The first group includes all the NMs a nd IM IIIs, all except 1 LGD, about half of HGDs, and 1 EGG. E-Cad is highl y expressed, MMP2 and angiogenesis are low, the proliferative activity is l ow and mitoses are partly balanced by apoptoses. The second group includes some EGCs and HGDs and is characterised by a very high proliferative activi ty and cell death; there is an initial loss of cell adhesion, an increase o f MMP2 and NV. The third group includes the majority of EGCs, but also 1 HG D: it has intermediate MI and AI, the lowest expression of E-Cad, the highe st expression of MMP2 and the most numerous microvessels. These results und erscore the necessity of evaluating each case individually within the same singular category of Correa's sequence. The use of kinetic and molecular pa rameters in addition to the morphological analysis may give important infor mation on the behaviour of the various lesions.