Cellular changes in the tumor microenvironment of human esophageal squamous cell carcinomas

The growth, invasiveness, and metastasis of human cancers are not only determined by the cancer cells but also by their microenvironment. The purpose of this study was to extend our previous studies and to examine the cellular changes in tumor microenvironment (stroma) of esophageal squamous cell carcinomas (ESCCs). The proliferative activity, cellular components, and angiogenesis status in different compartments (non-tumor stroma, tumor stroma, and tumor periphery stroma) of ESCCs were evaluated by immunohistochemistry. The results revealed a hyperproliferative rate labeled by Ki-67 in stromal cells in tumor area as compared with that in stromal cells in non-tumor area, which resulted in the increased densities of myofibroblasts (labeled by smooth muscle actin (SMA)-alpha), lymphocytes (labeled by CD3), macrophages (labeled by CD68), and the activation of angiogenesis characterized by increased microvessel density (MVD) and the increased expression of the proangiogenic factors (vascular endothelial growth factor and interleukin 8) in the tumor stroma. Further analysis showed that the changes of stromal cell density were more significant in the area of periphery tumor stroma than that of stroma between tumor nests. Most cellular changes were significantly associated with lymph node involvement. Double immunohistochemistries with PCNA/CD3, PCNA/CD68, and PCNA/SMA-alpha revealed that these cells present in the ESCC tumor stroma had a proliferative capacity. The cells present in the tumor microenvironment of ESCCs were greatly activated, suggesting that microenvironmental components may be involved in the cancer growth and progression.