Expression of vascular endothelial growth factor C and chemokine receptor CCR7 in gastric carcinoma and their values in predicting lymph node metastasis

Abstract

AIM:To study the expression of vascular endothelial growth factor C (VEGF-C) and chemokine receptor CCR7 in gastric carcinoma and to investigate their associations with lymph node metastasis of gastric carcinoma and their values in predicting lymph node metastasis. METHODS:The expression of VEGF-C and CCR7 in gastric carcinoma tissues obtained from 118 patients who underwent curative gastrectomy was examined by immunohistochemistry. Among these patients, 39 patients underwent multi-slice spiral CT (MSCT) examination. RESULTS:VEGF-C and CCR7 were positively expressed in 52.5 and 53.4% of patients. VEGF-C expression was more frequently found in tumors with lymph node metastasis than those without it (P<0.001). VEGF-C expression was also closely related to lymphatic invasion (P<0.001), vascular invasion (P<0.01), and TNM stage (P<0.001). However, there was no significant correlation between VEGF-C expression and age at surgery, gender, tumor size, tumor location, Lauren classification, and depth of invasion. CCR7 expression was significantly higher in patients with lymph node metastasis compared with those without lymph node metastasis (P<0.001) and was also associated with tumor size (P<0.01), depth of invasion (P<0.001), lymphatic invasion (P<0.001), and TNM stage (P<0.001). However, the presence of CCR7 had no correlation to age at surgery, gender, tumor location, Lauren classification, and vascular invasion. Among the 39 patients who underwent MSCT examination, only CCR7 expression was related to lymph node metastasis determined by MSCT (P<0.05). In the current retrospective study, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of VEGF-C and CCR7 expression in the diagnosis of lymph node metastasis for patients with gastric carcinoma were 73.8%, 70.2%, 72.6%, 71.4% and 72.0%, and 82.0%, 77.2%, 79.4%, 80.0% and 79.7%, respectively. After subdivision according to the combination of VEGF-C and CCR7 expression, receiver operating characteristic (ROC) analysis showed that the accuracy of the combined examination of VEGF-C and CCR7 expression in predicting lymph node metastasis was relatively high (area under ROC curve [Az]=0.83). CONCLUSION:The expression of VEGF-C and CCR7 is related to lymph node metastasis of gastric carcinoma and both of them may become new targets for the treatment of gastric carcinoma. Furthermore, the combined examination of VEGF-C and CCR7 expression in endoscopic biopsy specimens may be useful in predicting lymph node metastasis of gastric carcinoma and deciding the extent of surgical lymph node resection.

Chemokine-mediated migration of melanoma cells towards lymphatics – a mechanism contributing to metastasis

“…CCL21 (6Ckine, SLC) is a chemokine thought to be involved in recruitment of T cells and dendritic cells to lymph nodes and is expressed by the lymphatic vessels of many tissues (Gunn et al, 1998;Saeki et al, 1999). Recent reports have also shown that human (Takeuchi et al, 2004) and murine (Wiley et al, 2001) melanomas express CCR7, the receptor for CCL21 and CCL19 and that in gastric carcinoma, head and neck squamous cell carcinoma, non-small cell lung cancer and breast cancer these two factors may be associated with lymph node metastasis (Muller et al, 2001;Mashino et al, 2002;Takanami, 2003;Wang et al, 2004;Yan et al, 2004). In the present study, we showed that two different malignant melanoma cell lines can detect CCL21 in vitro through expression of its cognate receptor CCR7 on melanoma cells, as a result of which the melanoma cells migrated towards the source of the chemokine.…”

Expression of CC chemokine receptor 7 in tonsillar cancer predicts cervical nodal metastasis, systemic relapse and survival

“…Recent studies have suggested that normal chemokine signalling pathways that play a central role in lymphoid cell migration and homeostasis can be subverted in SCCHN (and other tumours) to mediate specific patterns of tumour spread. CC chemokine receptor 7 is known to influence the migration of activated dendritic cells to regional lymph nodes and appears to play a similar role in gastric, oesophageal and head and neck cancers (Mashino et al, 2002;Ding et al, 2003;Wang et al, 2004;Yan et al, 2004). Mashino et al (2002) showed that 66% of gastric carcinoma samples from 64 patients expressed CCR7 and those patients with CCR7-positive tumours had a significantly worse prognosis.…”

“…Subsequent studies have demonstrated that CCR7 appears to play an important role in the development of lymph node metastases from oesophageal and gastric cancers (Mashino et al, 2002;Ding et al, 2003;Yan et al, 2004). CC chemokine receptor 7 is also expressed by human adult T-cell leukaemia cells that lodge in lymph nodes (Hasegawa et al, 2000).…”

C‑C motif chemokine receptors in gastric cancer (Review)

“…Numerous studies have shown that CCR7 is differentially expressed in tumor cells in gastric cancer at the mRNA and protein levels, as well as in the cell membrane in vitro and in vivo (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). In addition, CCR7 was detected in tumor-infiltrating lymphocytes and dendritic cells in gastric cancer, as well as in mononuclear cells in Helicobacter pylori gastritis (35,38).…”