Prediction of lymph node metastasis in colorectal carcinoma by expressionof chemokine receptor CCR7

Abstract

Chemokine receptors are known to regulate homing of lymphocytes into secondary lymphoid organs and may also be involved in the lymphatic spread of solid tumors. Therefore, the assessment of chemokine receptor expression on colorectal carcinomas could potentially improve the prediction of lymph node spread. This is of great importance for the selection of patients for local therapy without the need for concomitant lymphatic dissection. Currently, only 5% of all patients can be selected for this desirable treatment option by established prognosticators. In a retrospective study, expression levels of the chemokine receptors CCR7, CXCR4 and CXCR5 were determined by immunohistochemistry on paraffin-embedded specimens of 99 colorectal carcinomas, which were curatively operated on, comprising all stages of the disease. Receptor expressions (absent vs. positive) from the overall tumor (OT) and from the invasion front (IF) including further prognosticators were correlated with lymph node status by uni-and multivariate analysis. Data were also correlated with synchronous distant metastases and overall survival. Median follow-up was 64 months. In univariate analysis, lymph node status correlated significantly with lymphovascular invasion, the expression of CCR7 IF, CCR7 OT, CXCR4 IF and CXCR4 OT, as well as pT category. Multivariate analysis revealed a significant correlation of lymph node status with lymphovascular invasion and CCR7 IF expression level. Most interestingly, CCR7 IF expression was significantly linked to decreased survival. CCR7 plays an important role in the mechanism of lymph node spread in colorectal carcinoma. Evaluation of the chemokine receptor expression profile seems to be appropriate to improve the selection of patients suited for local treatment and might constitute targets for nonsurgical therapy. ' 2005 Wiley-Liss, Inc.

Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients

“…In one report, immunohistochemistry revealed CXCR5 expression in a significant proportion of human colon carcinoma specimens (Gunther et al, 2005), whereas another group demonstrated cytoplasmatic expression in pancreatic cancer cells and cell lines (Meijer et al, 2006). We show here for the first time that the ligand for CXCR5, CXCL13, is the most significantly overexpressed chemokine in breast cancer, supporting the idea of a role of CXCL13/CXCR5 interactions in promoting initiation and/or progression of this tumour type and, possibly, other human cancers.…”

Chemokines in cancer related inflammation

“…breast, melanoma, gastric, non-small cell lung cancer, head and neck tumors, colorectal carcinoma), CCR7 is upregulated and mediates tumor cell dissemination to lymph nodes [101][102][103][104][105][106]. In a recent study, brain infiltration by T-cell leukemic blasts was mediated by CCR7 [15].…”

Chemokines in tumor angiogenesis and metastasis

“…CCR7 plays a critical role in lymphocyte and dendritic cell trafficking into and within lymph nodes. Human cancer cells from malignant breast, gastric, oesophageal, NSCLC, squamous cell carcinoma of the head and neck and colorectal carcinomas express functional CCR7 [133,[165][166][167][168][169]. Cancer cells that over-express CCR7 can migrate towards its ligand CCL21, which is strongly expressed in lymph nodes [167,170].…”

“…Recently, it has been reported that CCR7 activation on thyroid carcinoma cell by CCL21 favors tissue invasion and cell proliferation, and therefore may promote thyroid carcinoma growth and lymph node metastasis [172]. CCR7 is a potential marker to predict metastasis in breast and colorectal cancer and is correlated with disease progression [138,166]. In addition, patients with oral and oropharyngeal squamous cell carcinomas that express CCR7 have lower survival rates than those with CCR7-negative tumors [173].…”