Diffuse Gastric Carcinoma Undergoes Characteristic Phenotypic Changes in the Intravascular Environment: Evidence for a Reversal of the Epithelial-Mesenchymal Transition in Lymphovascular Metastasis

Abstract

This article reports differences between the properties of extravascular carcinoma, which generally forms the vast bulk of a tumor, and those of intravascular carcinoma, at both primary and metastatic lymph node sites. In a morphological and immunohistochemical study of 19 diffuse gastric adenocarcinomas, we report that in comparison to extravascular carcinoma, the intravascular tumor compartment showed frequent and profound phenotypic change, including increased tumor cell cohesion, differentiation and cadherin/catenin expression. For example, greatest cohesion was seen at the intravascular site in 78% (P = .00006) of primary cancers and in 84% (P = .000015) of their lymph node metastases. Pan cadherin showed a statistically significant increase at the intravascular metastatic site (P = .031). We suggest that this change from an extravascular isolated cell phenotype to an intravascular cohesive phenotype represents reversal of the epithelial to mesenchymal transition. Since this proposed reversal of epithelial to mesenchymal transition in intravascular carcinoma is frequently conspicuous in routine histological sections of many types of cancer, as our previous publications have indicated, this process is likely to have widespread significance for the biology of metastasis.