Characterization of Tumor Angiogenesis in Gastric Carcinomas at Different Stages of Their Progression

Abstract

Introduction. The biological behavior of the tumor largely depends on the characteristics of the vascular bed and previous tumor angiogenesis models. Studying the morphology of vessels allows not only to improve the prediction of early metastasis, but also to develop more effective treatment methods.

Materials and methods. We studied 55 cases of gastric cancer (GC) of various histological structures according to the the Laurén classification. Immunohistochemical study was performed using antibodies to pancytokeratin AE1/AE3, cytokeratins 17, 18, vimentin, E-cadherin, alpha-smooth muscle actin (α-SMA), CD31, CD34, Ki67. The length, morphology and density of the tumor vascular bed, the number, nature and features of the stroma were assessed. Morphological signs of epithelial-mesenchymal transition (EMT), the completeness and prevalence of this process in the tumor were identified and compared with angiogenesis.

Results. There are few pre-existing vessels with fully constructed walls in the intestinal-type tumor. The analysis revealed a pronounced polymorphism, with predominantly sinusoidal, thin-walled blood vessels. Cases with high vascular density prevail. We did not find any correlation between vascular bed density and tumor stage (p = 0.779 by chi-square test). Focal incomplete EMT prevails in the tumor. There are few pre-existing vessels with full walls in diffuse GC. In part of the vessels, the endothelium expressed CD34 without expressing CD31. There are no signs of proliferative activity in the endothelium. In all cases, EMT is more often widespread and incomplete; complete EMT is less common. The vessels structure varies in mixed tumors, with few having a fully constructed wall. More often, the vessels had the structure of sinusoids, thin-walled with irregularly shaped openings. In mixed GC, bed density was higher in areas of undifferentiated cancer compared to well differentiated adenocarcinoma. Cases with focal incomplete EMT predominate.

Conclusion. The vessels are characterized by great morphological, functional, and immunomorphological diversity, which affects the tumor behavior. In intestinal-type GC, tumor invasion is influenced to a greater extent by the density of the bed, and less by the prevalence and completeness of EMT. In diffuse-type GC, vessel density plays a lesser role in invasion than the prevalence of EMT, as well as the higher frequency of complete EMT. In mixed GC, vascular invasion is influenced by the high density of the vascular bed and the completeness of the EMT.