Tumor-associated macrophages and angiogenesis in early stage esophageal squamous cell carcinoma
- 212 Downloads
The association between angiogenesis and tumor-associated macrophages (TAMs) is unclear. Mononuclear cell infiltration was reported to induce angiogenesis in early stage esophageal squamous cell carcinoma (ESCC).
The study materials included 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer (M1 and M2 cancer 27; M3 or deeper cancer 37). We assessed microvessel density (MVD) using CD34 and CD105 immunostaining and monocyte count (MC) using CD68 and CD163 immunostaining in relation to the histological type or grade of mononuclear cell infiltration, as well as the correlation between MVD and MC.
MVD and MC increased in accordance with histological type, and the differences were significant (P < 0.001). MVD and MC were significantly higher in M1 and M2 lesions than in normal squamous epithelium (P < 0.05). MVD (CD34 and CD105) and MC (CD68 and CD163) were significantly correlated with the degree of mononuclear cell infiltration (P < 0.001), and there was a strong correlation between MC assessed using CD68 and MC assessed using CD163 (rS = 0.93, P < 0.001). The CD163/CD68 ratio did not differ significantly according to histological type. There was a significant correlation between MVD assessed using CD105 and MC assessed using CD68 (rS = 0.69, P < 0.001) and CD163 (rS = 0.67, P < 0.001). MVD assessed using CD34 was also significantly correlated with MC assessed using both CD68 (rS = 0.59, P < 0.001) and CD163 (rS = 0.57, P < 0.001).
The number of TAMs is significantly associated with the development of neovasculature in the early stage of ESCC progression.
KeywordsMicrovessel density Monocyte count Tumor-associated macrophage Esophageal cancer Angiogenesis
Carcinoma in situ
Tumor invasion to the lamina propria mucosae
Tumor invasion to the muscularis mucosa
Tumor invasion to the upper third of the submucosal layer
Tumor invasion to the middle third of the submucosal layer
Tumor invasion to the lower third of the submucosal layer
Esophageal squamous cell carcinoma
Low-grade intraepithelial neoplasia (borderline malignancy)
This study was supported by MEXT KAKENHI Grant number 26461047.
Compliance with ethical standards
Conflict of interest
Youichi Kumagai received a research grant from MEXT KAKENHI.
Human rights statement and informed consent
All procedures followed were in accordance with the ethical standards of the committees responsible for human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent for inclusion of tissue samples in this study was obtained from all patients or their representatives.