Tumor angiogenesis in gastric cancer

Abstract

Gastric cancer (GC) is still a major health problem, being one of the leading causes of cancer-related death in the world. Although the overall incidence of GC is decreasing in the United States and Western Europe, it is still high in many countries from Asia, South America, and Eastern Europe. The process of angiogenesis or the formation of new blood vessels plays an important role in cancer progression, as it allows oxygen supply, nutrients, and factors to grow tumor cells. In our study, we found that gastric neoplasms have high vascularity, with anarchic distribution, uneven in tumor stroma, sometimes with congestion vessels and microhemorrhages. Most vessels were capillaries, with a discontinuous endothelium, poorly structured basement membrane, without junctions between endothelial cells, hyperpermeable, creating the possibility of local edema in the tumor microenvironment (TME), and also extravasation of the plasma, leukocytes and even red blood cells. Angiogenesis vessels showed a low number of pericytes, which shows that they are young vessels, both morphologically and functionally immature. Tumor cells can synthesize biochemical factors [vascular endothelial growth factor-A (VEGF-A)] that stimulate the formation of new vessels (angiogenesis) to ensure their growth and metastasis. Some connective cells (tumor-associated mast cells, tumor-associated fibroblasts) are also involved in the angiogenesis process, which stimulate the progression of tumor cells and remodel the TME.

Figure 1

Moderately differentiated gastric adenocarcinoma with numerous blood vessels in the stroma. Hematoxylin–Eosin (HE) staining, ×100

Figure 2

Tumoral stroma with moderate chronic inflammatory, vascular congestion and microhemorrhagic foci. HE staining, ×100.

Figure 3

Moderately differentiated gastric adenocarcinoma with numerous angiogenesis vessels spread unevenly in the tumor microenvironment. Immunomarking with anti-CD34 antibody, ×100. CD34: Cluster of differentiation 34

Figure 4

Detailed picture of tumor angiogenesis capillaries. Discontinuity of the endothelial wall, lack of pericytes, highly variable lumen and even angioblastic cords without lumen are observed. Immunomarking with anti-CD34 antibody, ×400

Figure 5

Well-differentiated gastric adenocarcinoma with angiogenesis capillaries arranged near tumor cells. Immunomarking with anti-CD34 antibody, ×200.

Figure 6

Well-differentiated gastric adenocarcinoma area with strongly infiltrated stroma with inflammatory cells and numerous transversely sectioned angiogenesis capillaries. Immunomarking with anti-CD34 antibody, ×200

Figure 7

Poorly differentiated gastric adenocarcinoma with an increased number of angiogenesis vessels and CD34-positive isolated cells in the tumor microenvironment. Immunomarking with anti-CD34 antibody, ×200

Figure 8

Tumor stroma with desmoplastic transformation, with many angiogenesis capillaries. Immunomarking with anti-CD34 antibody, ×100

Figure 9

Well-differentiated gastric adenocarcinoma with moderate reaction to VEGF-A. Immunomarking with anti-VEGF-A antibody, ×200. VEGF-A: Vascular endothelial growth factor-A

Figure 10

Poorly differentiated gastric adenocarcinoma with intense reaction to VEGF-A. Immunomarking with anti-VEGF-A antibody, ×200

Figure 11

Undifferentiated gastric adenocarcinoma with numerous mast cells in the tumoral stroma. Immunomarking with anti-tryptase antibody, ×200.

Figure 12

Well-differentiated gastric adenocarcinoma with a high number of mast cells in the tumoral stroma. Immunomarking with anti-tryptase antibody, ×100

Figure 13

Moderately differentiated gastric adenocarcinoma with numerous neoformation vessels and numerous cancer-associated fibroblasts, intensely positive to α-SMA. Immunomarking with anti-α-SMA antibody, ×100. α-SMA: Alpha-smooth muscle actin.

Figure 14

Gastric tumoral stroma with myofibroblastic conjunctive cells intensely positive to α-SMA. Immunomarking with anti-α-SMA antibody, ×100